斑马鱼早期胚胎发育时期染色质可及性动态研究

合子基因组激活（ZGA）和细胞命运决定的分子机制是胚胎发育过程中的两个重要研究内容。ZGA涉及到大量基因激活，合子基因组由沉默转变为活跃状态，产生了大量合子转录本。细胞命运决定是指细胞在发育过程中逐渐丢失全能性，开始分化成特定的细胞类型，这些细胞类型共同构成了一个结构、功能完整的个体。上述发育事件中，染色质状态在基因表达调控中起重要作用，其紧密程度直接影响基因的转录活性。由于胚胎细胞在发育过程中的异质性和非同步性，而单细胞测序技术是研究细胞异质性和基因调控网络的有效手段。通过单细胞染色质可及性测序技术，研究人员可以在单个细胞水平上分析染色质可及性，发现细胞之间的差异和发育中染色质的动态。目前，关于斑马鱼胚胎发育早期的染色质可及性特征尚不明确，染色质可及性同ZGA和细胞命运决定之间的调控关系尚不清楚，仍缺乏这一阶段的单细胞染色质可及性数据。本研究开发优化了单细胞染色质可及性测序技术，探究斑马鱼早期胚胎发育中染色质可及性的变化特征，以及这些变化对ZGA和细胞命运决定的影响。

以孔板法为技术基础，本研究优化了单细胞核染色质可及性测序（snATAC-seq）和开发了单胚胎单细胞染色质可及性测序（sescATAC-seq）两种适用于斑马鱼胚胎细胞的单细胞测序技术。测序所需的起始细胞投入量和文库的线粒体DNA含量降低，方法稳定可靠，所构建的文库质量良好。本研究成功构建了斑马鱼胚胎受精后2小时至4.3小时的单细胞染色质可及性文库。本研究收集超过10,000个细胞的数据，绘制了斑马鱼早期胚胎的单细胞染色质可及性图谱。

研究结果揭示了斑马鱼早期胚胎发育过程中染色质可及性的动态变化，这些变化与基因表达调控密切相关。在受精后2小时，染色质可及性首次被检测到。本研究获得了多组peak modules，这些modules代表了基因组中特定区域的染色质状态变化。发育上升型modules与发育过程中活跃的基因调控区域相关，而发育下降型modules与转座元件LTR（长末端重复序列）相关。整体变化趋势是，TSS（转录起始位点）区域的可及性增强，部分基因间LTR区域的可及性降低。

本研究发现，在受精后4.1小时，斑马鱼胚胎首次出现细胞异质性。根据染色质可及性的差异，细胞被划分为4个细胞簇：DEL 1、DEL 2、EVL和YSL。4个细胞簇的特征分别与囊胚细胞、胚外包膜层和卵黄合胞层相对应，这与胚胎在该阶段的结构特征吻合。每个细胞簇的基因相关区域的可及性活性差异反映了它们的状态独特性，与细胞的特定功能和空间定位有关。特别值得注意的是，YSL细胞簇在以往的转录组数据中未被报道，但在本研究的染色质可及性检测中被揭示。拟时序分析显示了细胞簇在时序中的特征和状态转变，揭示了4个细胞簇（DEL 1、DEL 2、EVL和YSL）在发育过程中的分化轨迹。分析结果显示，4个细胞簇在拟时序上具有明确的分化关系。分化过程以DEL 1为起点，随后依次形成了EVL、DEL 2和YSL细胞簇。DEL 1是最早期的细胞状态，其他细胞簇是在此基础上进一步分化的结果。此外，本研究采用了一套综合的方法来识别基因组中具有细胞类型特异性的增强子区域。基于识别区域的染色质可及性水平、与启动子的距离、已知的调控元件特征，研究筛选出具有高生物学潜力的增强子区域，并在体内验证识别区域的功能。

本研究的创新性成果如下：第一，开发了低投入量的单细胞染色质可及性测序方法，降低了起始的细胞投入量和线粒体DNA含量。第二，绘制了斑马鱼2 h.p.f-4.3 h.p.f阶段单细胞染色质可及性图谱（细胞数量超过10,000个），揭示了早期发育过程中染色质可及性的变化和特征，填补了现有研究的数据空白。第三，发现斑马鱼胚胎4.1 h.p.f阶段呈现4个细胞簇，阐明了它们的染色质可及性特征及调控机制，揭示了4个细胞簇的细胞分化轨迹，发现了EVL和YSL特异性的增强子。

本研究揭示了斑马鱼早期胚胎发育过程的染色质可及性调控机制，以及它们对基因调控的作用。本研究能够增进人们对胚胎发育基本机制的理解，为理解斑马鱼早期胚胎发育过程中的表观遗传调控机制提供了宝贵信息。同时，本研究揭示了不同细胞类型在发育中的染色质状态变化，以及这些变化如何与细胞命运决定相关。此外，还揭示了新的调控元件（如增强子），以及它们在胚胎发育中的作用。本研究的内容对于发育生物学的研究和基因转录调控的理解具有重要意义。

[1] KLEMM S L, SHIPONY Z, GREENLEAF W J. Chromatin accessibility and the regulatory epigenome[J]. Nature Reviews Genetics, 2019, 20(4): 207-220.
[2] THURMAN R E, RYNES E, HUMBERT R, et al. The accessible chromatin landscape of the human genome[J]. Nature, 2012, 489(7414): 75-82.
[3] ANDERSSON R, SANDELIN A. Determinants of enhancer and promoter activities of regulatory elements[J]. Nature Reviews Genetics, 2020, 21(2): 71-87.
[4] SPITZ F, FURLONG E E. Transcription factors: from enhancer binding to developmental control[J]. Nature Reviews Genetics, 2012, 13(9): 613-626.
[5] SCHOENFELDER S, FRASER P. Long-range enhancer-promoter contacts in gene expression control[J]. Nature Reviews Genetics, 2019, 20(8): 437-455.
[6] BANERJI J, RUSCONI S, SCHAFFNER W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences[J]. Cell, 1981, 27(2 Pt 1): 299-308.
[7] ABDULGHANI M, JAIN A, TUTEJA G. Genome-wide identification of enhancer elements in the placenta[J]. Placenta, 2019, 79: 72-77.
[8] RAZIN S V, ULIANOV S V, IAROVAIA O V. Enhancer Function in the 3D Genome[J]. Genes (Basel), 2023, 14(6)
[9] NARITA T, HIGASHIJIMA Y, KILIC S, et al. Acetylation of histone H2B marks active enhancers and predicts CBP/p300 target genes[J]. Nature Genetics, 2023, 55(4): 679-692.
[10] WANG Y, ZHANG C, WANG Y, et al. Enhancer RNA (eRNA) in Human Diseases[J]. Int J Mol Sci, 2022, 23(19)
[11] ANDERSSON R, GEBHARD C, MIGUEL-ESCALADA I, et al. An atlas of active enhancers across human cell types and tissues[J]. Nature, 2014, 507(7493): 455-+.
[12] SCHWALB B, MICHEL M, ZACHER B, et al. TT-seq maps the human transient transcriptome[J]. Science, 2016, 352(6290): 1225-1228.
[13] CONSORTIUM E P, MOORE J E, PURCARO M J, et al. Expanded encyclopaedias of DNA elements in the human and mouse genomes[J]. Nature, 2020, 583(7818): 699-710.
[14] NORD A S, BLOW M J, ATTANASIO C, et al. Rapid and pervasive changes in genome-wide enhancer usage during mammalian development[J]. Cell, 2013, 155(7): 1521-1531.
[15] CORCES M R, BUENROSTRO J D, WU B, et al. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution[J]. Nature Genetics, 2016, 48(10): 1193-1203.
[16] O'FARRELL P H. Growing an Embryo from a Single Cell: A Hurdle in Animal Life[J]. Cold Spring Harb Perspect Biol, 2015, 7(11)
[17] TADROS W, LIPSHITZ H D. The maternal-to-zygotic transition: a play in two acts[J]. Development, 2009, 136(18): 3033-3042.
[18] HARVEY E B. Development of half-eggs of Chaetopterus pergamentaceus with special reference to parthenogenetic merogony[J]. Biological Bulletin, 1939, 76(3): 384-404.
[19] YUAN S L, ZHAN J H, ZHANG J Y, et al. Human zygotic genome activation is initiated from paternal genome[J]. Cell Discovery, 2023, 9(1)
[20] JUKAM D, SHARIATI S A M, SKOTHEIM J M. Zygotic Genome Activation in Vertebrates[J]. Dev Cell, 2017, 42(4): 316-332.
[21] COLLART C, OWENS N D L, BHAW-ROSUN L, et al. High-resolution analysis of gene activity during the Xenopus mid-blastula transition[J]. Development, 2014, 141(9): 1927-1939.
[22] OWENS N D L, BLITZ I L, LANE M A, et al. Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development[J]. Cell Reports, 2016, 14(3): 632-647.
[23] IWAO Y, UCHIDA Y, UENO S, et al. Midblastula transition (MBT) of the cell cycles in the yolk and pigment granule-free translucent blastomeres obtained from centrifuged Xenopus embryos[J]. Development Growth & Differentiation, 2005, 47(5): 283-294.
[24] HEYN P, KIRCHER M, DAHL A, et al. The earliest transcribed zygotic genes are short, newly evolved, and different across species[J]. Cell Rep, 2014, 6(2): 285-292.
[25] AANES H, WINATA C L, LIN C H, et al. Zebrafish mRNA sequencing deciphers novelties in transcriptome dynamics during maternal to zygotic transition[J]. Genome Res, 2011, 21(8): 1328-1338.
[26] YANG H X, ZHOU Y, GU J L, et al. Deep mRNA Sequencing Analysis to Capture the Transcriptome Landscape of Zebrafish Embryos and Larvae[J]. PLoS One, 2013, 8(6)
[27] MATHAVAN S, LEE S G P, MAK A, et al. Transcriptome analysis of zebrafish embryogenesis using microarrays[J]. Plos Genetics, 2005, 1(2): 260-276.
[28] FLACH G, JOHNSON M H, BRAUDE P R, et al. The transition from maternal to embryonic control in the 2-cell mouse embryo[J]. Embo j, 1982, 1(6): 681-686.
[29] AOKI F, WORRAD D M, SCHULTZ R M. Regulation of transcriptional activity during the first and second cell cycles in the preimplantation mouse embryo[J]. Dev Biol, 1997, 181(2): 296-307.
[30] HAMATANI T, CARTER M G, SHAROV A A, et al. Dynamics of global gene expression changes during mouse preimplantation development[J]. Dev Cell, 2004, 6(1): 117-131.
[31] YAN L, YANG M, GUO H, et al. Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells[J]. Nature Structural & Molecular Biology, 2013, 20(9): 1131-1139.
[32] XUE L, CAI J Y, MA J, et al. Global expression profiling reveals genetic programs underlying the developmental divergence between mouse and human embryogenesis[J]. BMC Genomics, 2013, 14: 568.
[33] KONG Q, YANG X, ZHANG H, et al. Lineage specification and pluripotency revealed by transcriptome analysis from oocyte to blastocyst in pig[J]. FASEB J, 2020, 34(1): 691-705.
[34] PRITCHARD D K, SCHUBIGER G. Activation of transcription in Drosophila embryos is a gradual process mediated by the nucleocytoplasmic ratio[J]. Genes & Development, 1996, 10(9): 1131-1142.
[35] LEFEBVRE F A, LECUYER E. Flying the RNA Nest: Drosophila Reveals Novel Insights into the Transcriptome Dynamics of Early Development[J]. Journal of Developmental Biology, 2018, 6(1)
[36] SWINBURNE I A, SILVER P A. Intron delays and transcriptional timing during development[J]. Developmental Cell, 2008, 14(3): 324-330.
[37] SHERMOEN A W, OFARRELL P H. Progression of the Cell-Cycle through Mitosis Leads to Abortion of Nascent Transcripts[J]. Cell, 1991, 67(2): 303-310.
[38] PERSSON J, EKWALL K. Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation[J]. Experimental Cell Research, 2010, 316(8): 1316-1323.
[39] HAN M H, ISSAGULOVA D, PARK M. Interplay between epigenome and 3D chromatin structure[J]. BMB Rep, 2023, 56(12): 633-644.
[40] MOORE L D, LE T, FAN G P. DNA Methylation and Its Basic Function[J]. Neuropsychopharmacology, 2013, 38(1): 23-38.
[41] BRAUN R E. Packaging paternal chromosomes with protamine[J]. Nature Genetics, 2001, 28(1): 10-12.
[42] KIMMINS S, SASSONE-CORSI P. Chromatin remodelling and epigenetic features of germ cells[J]. Nature, 2005, 434(7033): 583-589.
[43] BRYKCZYNSKA U, HISANO M, ERKEK S, et al. Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa[J]. Nature Structural & Molecular Biology, 2010, 17(6): 679-687.
[44] VAN DE WERKEN C, VAN DER HEIJDEN G W, ELEVELD C, et al. Paternal heterochromatin formation in human embryos is H3K9/HP1 directed and primed by sperm-derived histone modifications[J]. Nature Communications, 2014, 5
[45] MHANNI A A, MCGOWAN R A. Global changes in genomic methylation levels during early development of the zebrafish embryo[J]. Dev Genes Evol, 2004, 214(8): 412-417.
[46] OSWALD J, ENGEMANN S, LANE N, et al. Active demethylation of the paternal genome in the mouse zygote[J]. Curr Biol, 2000, 10(8): 475-478.
[47] SANTOS F, HENDRICH B, REIK W, et al. Dynamic reprogramming of DNA methylation in the early mouse embryo[J]. Developmental Biology, 2002, 241(1): 172-182.
[48] SMITH Z D, CHAN M M, MIKKELSEN T S, et al. A unique regulatory phase of DNA methylation in the early mammalian embryo[J]. Nature, 2012, 484(7394): 339-344.
[49] STANCHEVA I, EL-MAARRI O, WALTER J, et al. DNA methylation at promoter regions regulates the timing of gene activation in Xenopus laevis embryos[J]. Developmental Biology, 2002, 243(1): 155-165.
[50] POTOK M E, NIX D A, PARNELL T J, et al. Reprogramming the maternal zebrafish genome after fertilization to match the paternal methylation pattern[J]. Cell, 2013, 153(4): 759-772.
[51] KOBAYASHI W, TACHIBANA K. Awakening of the zygotic genome by pioneer transcription factors[J]. Curr Opin Struct Biol, 2021, 71: 94-100.
[52] SCHULZ K N, BONDRA E R, MOSHE A, et al. Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo[J]. Genome Research, 2015, 25(11): 1715-1726.
[53] LIANG H L, NIEN C Y, LIU H Y, et al. The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila[J]. Nature, 2008, 456(7220): 400-U467.
[54] RIBEIRO L, TOBIAS-SANTOS V, SANTOS D, et al. Evolution and multiple roles of the Pancrustacea specific transcription factor zelda in insects[J]. Plos Genetics, 2017, 13(7): e1006868.
[55] DUAN J, RIEDER L, COLONNETTA M M, et al. CLAMP and Zelda function together to promote Drosophila zygotic genome activation[J]. Elife, 2021, 10
[56] GASKILL M M, GIBSON T J, LARSON E D, et al. GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo[J]. Elife, 2021, 10
[57] PALFY M, SCHULZE G, VALEN E, et al. Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation[J]. Plos Genetics, 2020, 16(1): e1008546.
[58] VEIL M, YAMPOLSKY L Y, GRÜNING B, et al. Pou5f3, SoxB1, and Nanog remodel chromatin on high nucleosome affinity regions at zygotic genome activation[J]. Genome Res, 2019, 29(3): 383-395.
[59] GAGNON J A, OBBAD K, SCHIER A F. The primary role of zebrafish nanog is in extra-embryonic tissue[J]. Development, 2018, 145(1)
[60] POWNALL M E, MIAO L Y, VEJNAR C E, et al. Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin[J]. Science, 2023, 381(6653): 92-99.
[61] STANNEY W, 3RD, LADAM F, DONALDSON I J, et al. Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish[J]. Dev Biol, 2020, 459(2): 161-180.
[62] MEIER M, GRANT J, DOWDLE A, et al. Cohesin facilitates zygotic genome activation in zebrafish[J]. Development, 2018, 145(1)
[63] PRADHAN S J, REDDY P C, SMUTNY M, et al. Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis[J]. Nature Communications, 2021, 12(1)
[64] COLLART C, ALLEN G E, BRADSHAW C R, et al. Titration of Four Replication Factors Is Essential for the Xenopus laevis Midblastula Transition[J]. Science, 2013, 341(6148): 893-896.
[65] LU F, LIU Y, INOUE A, et al. Establishing Chromatin Regulatory Landscape during Mouse Preimplantation Development[J]. Cell, 2016, 165(6): 1375-1388.
[66] GAO L, WU K, LIU Z, et al. Chromatin Accessibility Landscape in Human Early Embryos and Its Association with Evolution[J]. Cell, 2018, 173(1): 248-259 e215.
[67] DE IACO A, PLANET E, COLUCCIO A, et al. DUX-family transcription factors regulate zygotic genome activation in placental mammals[J]. Nature Genetics, 2017, 49(6): 941-+.
[68] CHEN Z Y, ZHANG Y. Loss of DUX causes minor defects in zygotic genome activation and is compatible with mouse development[J]. Nature Genetics, 2019, 51(6): 947-+.
[69] ABBASSI L, MALKI S, COCKBURN K, et al. Multiple Mechanisms Cooperate to Constitutively Exclude the Transcriptional Co-Activator YAP from the Nucleus During Murine Oogenesis[J]. Biol Reprod, 2016, 94(5): 102.
[70] GASSLER J, KOBAYASHI W, GASPAR I, et al. Zygotic genome activation by the totipotency pioneer factor Nr5a2[J]. Science, 2022, 378(6626): 1305-1315.
[71] WU J, HUANG B, CHEN H, et al. The landscape of accessible chromatin in mammalian preimplantation embryos[J]. Nature, 2016, 534(7609): 652-657.
[72] JI S, CHEN F, STEIN P, et al. OBOX regulates murine zygotic genome activation and early development[J]. Nature, 2023
[73] FALCO G, LEE S L, STANGHELLINI I, et al. Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells[J]. Dev Biol, 2007, 307(2): 539-550.
[74] WANG C, CHEN C, LIU X, et al. Dynamic nucleosome organization after fertilization reveals regulatory factors for mouse zygotic genome activation[J]. Cell Res, 2022, 32(9): 801-813.
[75] ZHAO Y, ZHAI Y, FU C, et al. Transcription factor ELK1 regulates the expression of histone 3 lysine 9 to affect developmental potential of porcine preimplantation embryos[J]. Theriogenology, 2023, 206: 170-180.
[76] JIANG W J, SUN M H, LI X H, et al. Y-box binding protein 1 influences zygotic genome activation by regulating N6-methyladenosine in porcine embryos[J]. J Cell Physiol, 2023, 238(7): 1592-1604.
[77] LI X H, SUN M H, JIANG W J, et al. ZSCAN4 Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos[J]. Int J Mol Sci, 2023, 24(15)
[78] CHO T, SAKAI S, NAGATA M, et al. Involvement of chromatin structure in the regulation of mouse zygotic gene activation[J]. Animal Science Journal, 2002, 73(2): 113-122.
[79] NIU L, SHEN W, SHI Z, et al. Three-dimensional folding dynamics of the Xenopus tropicalis genome[J]. Nature Genetics, 2021, 53(7): 1075-1087.
[80] KAAIJ L J T, VAN DER WEIDE R H, KETTING R F, et al. Systemic Loss and Gain of Chromatin Architecture throughout Zebrafish Development[J]. Cell Rep, 2018, 24(1): 1-10.e14.
[81] WIKE C L, GUO Y X, TAN M Y, et al. Chromatin architecture transitions from zebrafish sperm through early embryogenesis[J]. Genome Research, 2021, 31(6): 981-994.
[82] GALITSYNA A, ULIANOV S V, BYKOV N S, et al. Extrusion fountains are hallmarks of chromosome organization emerging upon zygotic genome activation[J]. bioRxiv, 2023
[83] PATEL L, KANG R, ROSENBERG S C, et al. Dynamic reorganization of the genome shapes the recombination landscape in meiotic prophase[J]. Nature Structural & Molecular Biology, 2019, 26(3): 164-174.
[84] DU Z H, ZHENG H, HUANG B, et al. Allelic reprogramming of 3D chromatin architecture during early mammalian development[J]. Nature, 2017, 547(7662): 232-+.
[85] CHEN X, KE Y, WU K, et al. Key role for CTCF in establishing chromatin structure in human embryos[J]. Nature, 2019, 576(7786): 306-310.
[86] BORGEL J, GUIBERT S, LI Y, et al. Targets and dynamics of promoter DNA methylation during early mouse development[J]. Nature Genetics, 2010, 42(12): 1093-1100.
[87] BOGDANOVIC O, LONG S W, VAN HEERINGEN S J, et al. Temporal uncoupling of the DNA methylome and transcriptional repression during embryogenesis[J]. Genome Res, 2011, 21(8): 1313-1327.
[88] ANDERSEN I S, REINER A H, AANES H, et al. Developmental features of DNA methylation during activation of the embryonic zebrafish genome[J]. Genome Biol, 2012, 13(7): R65.
[89] STANCHEVA I, MEEHAN R R. Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos[J]. Genes Dev, 2000, 14(3): 313-327.
[90] CHEN F, LI M G, HUA Z D, et al. TET Family Members Are Integral to Porcine Oocyte Maturation and Parthenogenetic Pre-Implantation Embryogenesis[J]. Int J Mol Sci, 2023, 24(15)
[91] LI X Y, HARRISON M M, VILLALTA J E, et al. Establishment of regions of genomic activity during the Drosophila maternal to zygotic transition[J]. Elife, 2014, 3
[92] CHEN K, JOHNSTON J, SHAO W Q, et al. A global change in RNA polymerase II pausing during the Drosophila midblastula transition[J]. Elife, 2013, 2
[93] ZHANG B, WU X, ZHANG W, et al. Widespread Enhancer Dememorization and Promoter Priming during Parental-to-Zygotic Transition[J]. Mol Cell, 2018, 72(4): 673-686.e676.
[94] ZHANG B J, WU X T, ZHANG W H, et al. Widespread Enhancer Dememorization and Promoter Priming during Parental-to-Zygotic Transition[J]. Molecular Cell, 2018, 72(4): 673-+.
[95] LINDEMAN L C, ANDERSEN I S, REINER A H, et al. Prepatterning of Developmental Gene Expression by Modified Histones before Zygotic Genome Activation[J]. Developmental Cell, 2011, 21(6): 993-1004.
[96] DAHL J A, JUNG I, AANES H, et al. Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition[J]. Nature, 2016, 537(7621): 548-552.
[97] XIA W K, XU J W, YU G, et al. Resetting histone modifications during human parental-to-zygotic transition[J]. Science, 2019, 365(6451): 353-+.
[98] CHEN Z, DJEKIDEL M N, ZHANG Y. Distinct dynamics and functions of H2AK119ub1 and H3K27me3 in mouse preimplantation embryos[J]. Nature Genetics, 2021, 53(4): 551-563.
[99] MEI H, KOZUKA C, HAYASHI R, et al. H2AK119ub1 guides maternal inheritance and zygotic deposition of H3K27me3 in mouse embryos[J]. Nature Genetics, 2021, 53(4): 539-550.
[100] YEZHANG ZHU J Y, YAN RONG, YUN-WEN WU, YANG LI, LEJIAO ZHANG, YINGHAO PAN, HENG-YU FAN, LI SHEN,. Genomewide decoupling of H2AK119ub1 and H3K27me3 in early mouse development,[J]. Science Bulletin, 2021, Volume 66, Issue 24: 2489-2497.
[101] HICKEY G J M, WIKE C, NIE X, et al. Establishment of Developmental Gene Silencing by Ordered Polycomb Complex Recruitment in Early Zebrafish Embryos[J]. bioRxiv, 2021: 2021.2003.2016.435592.
[102] BERNSTEIN B E, MIKKELSEN T S, XIE X, et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells[J]. Cell, 2006, 125(2): 315-326.
[103] WU K L, FAN D D, ZHAO H, et al. Dynamics of histone acetylation during human early embryogenesis[J]. Cell Discovery, 2023, 9(1)
[104] CAO X, MA T, FAN R, et al. Broad H3K4me3 Domain Is Associated with Spatial Coherence during Mammalian Embryonic Development[J]. bioRxiv, 2023: 2023.2012.2011.570452.
[105] BU G, ZHU W, LIU X, et al. Coordination of zygotic genome activation entry and exit by H3K4me3 and H3K27me3 in porcine early embryos[J]. Genome Res, 2022, 32(8): 1487-1501.
[106] WU J, XU J, LIU B, et al. Chromatin analysis in human early development reveals epigenetic transition during ZGA[J]. Nature, 2018, 557(7704): 256-260.
[107] ZHANG B, ZHENG H, HUANG B, et al. Allelic reprogramming of the histone modification H3K4me3 in early mammalian development[J]. Nature, 2016, 537(7621): 553-557.
[108] NEWPORT J, KIRSCHNER M. A major developmental transition in early Xenopus embryos: I. characterization and timing of cellular changes at the midblastula stage[J]. Cell, 1982, 30(3): 675-686.
[109] NEWPORT J, KIRSCHNER M. A major developmental transition in early Xenopus embryos: II. Control of the onset of transcription[J]. Cell, 1982, 30(3): 687-696.
[110] JUKAM D, KAPOOR R R, STRAIGHT A F, et al. The DNA-to-cytoplasm ratio broadly activates zygotic gene expression in Xenopus[J]. Curr Biol, 2021, 31(19): 4269-4281 e4268.
[111] DEKENS M P S, PELEGRI F J, MAISCHEIN H M, et al. The maternal-effect gene futile cycle is essential for pronuclear congression and mitotic spindle assembly in the zebrafish zygote[J]. Development, 2003, 130(17): 3907-3916.
[112] LU X M, LI J M, ELEMENTO O, et al. Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition[J]. Development, 2009, 136(12): 2101-2110.
[113] CHAN S H, TANG Y, MIAO L, et al. Brd4 and P300 Confer Transcriptional Competency during Zygotic Genome Activation[J]. Dev Cell, 2019, 49(6): 867-881 e868.
[114] SCHULZ K N, HARRISON M M. Mechanisms regulating zygotic genome activation[J]. Nature Reviews Genetics, 2019, 20(4): 221-234.
[115] JOSEPH S R, PÁLFY M, HILBERT L, et al. Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos[J]. Elife, 2017, 6
[116] SHEN W, GONG B, XING C, et al. Comprehensive maturity of nuclear pore complexes regulates zygotic genome activation[J]. Cell, 2022, 185(26): 4954-4970 e4920.
[117] SCHOLER H R, DRESSLER G R, BALLING R, et al. Oct-4: a germline-specific transcription factor mapping to the mouse t-complex[J]. Embo j, 1990, 9(7): 2185-2195.
[118] NICHOLS J, ZEVNIK B, ANASTASSIADIS K, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4[J]. Cell, 1998, 95(3): 379-391.
[119] AVILION A A, NICOLIS S K, PEVNY L H, et al. Multipotent cell lineages in early mouse development depend on SOX2 function[J]. Genes Dev, 2003, 17(1): 126-140.
[120] CAO S, YU S, LI D, et al. Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency[J]. Cell Stem Cell, 2018, 22(4): 529-542 e525.
[121] DU Z, ZHANG K, XIE W. Epigenetic Reprogramming in Early Animal Development[J]. Cold Spring Harb Perspect Biol, 2021
[122] CONCHA M L, REIG G. Origin, form and function of extraembryonic structures in teleost fishes[J]. Philos Trans R Soc Lond B Biol Sci, 2022, 377(1865): 20210264.
[123] KIMMEL C B, WARGA R M, SCHILLING T F. Origin and organization of the zebrafish fate map[J]. Development, 1990, 108(4): 581-594.
[124] LACHNIT M, KUR E, DRIEVER W. Alterations of the cytoskeleton in all three embryonic lineages contribute to the epiboly defect of Pou5f1/Oct4 deficient MZ zebrafish embryos[J]. Developmental Biology, 2008, 315(1): 1-17.
[125] SABEL J L, D'ALENCON C, O'BRIEN E K, et al. Maternal Interferon Regulatory Factor 6 is required for the differentiation of primary superficial epithelia in and embryos[J]. Developmental Biology, 2009, 325(1): 249-262.
[126] KOTKAMP K, MOSSNER R, ALLEN A, et al. A Pou5f1/Oct4 dependent Klf2a, Klf2b, and Klf17 regulatory sub-network contributes to EVL and ectoderm development during zebrafish embryogenesis[J]. Dev Biol, 2014, 385(2): 433-447.
[127] FARRELL J A, WANG Y, RIESENFELD S J, et al. Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis[J]. Science, 2018, 360(6392)
[128] KRENS S F G, MÖLLMERT S, HEISENBERG C P. Enveloping cell-layer differentiation at the surface of zebrafish germ-layer tissue explants[J]. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(3): E9-E10.
[129] WILLIAMS D W, MULLER F, LAVENDER F L, et al. High transgene activity in the yolk syncytial layer affects quantitative transient expression assays in zebrafish Danio rerio) embryos[J]. Transgenic Res, 1996, 5(6): 433-442.
[130] CHEN S, KIMELMAN D. The role of the yolk syncytial layer in germ layer patterning in zebrafish[J]. Development, 2000, 127(21): 4681-4689.
[131] BETCHAKU T, TRINKAUS J P. Contact relations, surface activity, and cortical microfilaments of marginal cells of the enveloping layer and of the yolk syncytial and yolk cytoplasmic layers of fundulus before and during epiboly[J]. J Exp Zool, 1978, 206(3): 381-426.
[132] SIDDIQUI M, SHEIKH H, TRAN C, et al. The Tight Junction Component Claudin E is Required for Zebrafish Epiboly[J]. Developmental Dynamics, 2010, 239(2): 715-722.
[133] WHITE M D, ANGIOLINI J F, ALVAREZ Y D, et al. Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo[J]. Cell, 2016, 165(1): 75-87.
[134] WICKLOW E, BLIJ S, FRUM T, et al. HIPPO pathway members restrict SOX2 to the inner cell mass where it promotes ICM fates in the mouse blastocyst[J]. Plos Genetics, 2014, 10(10): e1004618.
[135] NIWA H, TOYOOKA T, SHIMOSATO D, et al. Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation[J]. Cell, 2005, 123(5): 917-929.
[136] HOME P, KUMAR R P, GANGULY A, et al. Genetic redundancy of GATA factors in the extraembryonic trophoblast lineage ensures the progression of preimplantation and postimplantation mammalian development[J]. Development, 2017, 144(5): 876-888.
[137] TORRES-PADILLA M E, PARFITT D E, KOUZARIDES T, et al. Histone arginine methylation regulates pluripotency in the early mouse embryo[J]. Nature, 2007, 445(7124): 214-218.
[138] WHITE M D, BISSIERE S, ALVAREZ Y D, et al. Mouse Embryo Compaction[J]. Curr Top Dev Biol, 2016, 120: 235-258.
[139] GOOLAM M, SCIALDONE A, GRAHAM S J L, et al. Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos[J]. Cell, 2016, 165(1): 61-74.
[140] SAKAUE M, OHTA H, KUMAKI Y, et al. DNA Methylation Is Dispensable for the Growth and Survival of the Extraembryonic Lineages[J]. Current Biology, 2010, 20(16): 1452-1457.
[141] AL-MOUSAWI J, BOSKOVIC A. Transcriptional and epigenetic control of early life cell fate decisions[J]. Curr Opin Oncol, 2022, 34(2): 148-154.
[142] YAO C, ZHANG W, SHUAI L. The first cell fate decision in pre-implantation mouse embryos[J]. Cell Regen, 2019, 8(2): 51-57.
[143] NISHIOKA N, INOUE K, ADACHI K, et al. The Hippo Signaling Pathway Components Lats and Yap Pattern Tead4 Activity to Distinguish Mouse Trophectoderm from Inner Cell Mass[J]. Developmental Cell, 2009, 16(3): 398-410.
[144] FRUM T, WATTS J L, RALSTON A. TEAD4, YAP1 and WWTR1 prevent the premature onset of pluripotency prior to the 16-cell stage[J]. Development, 2019, 146(17)
[145] LEUNG C Y, ZERNICKA-GOETZ M. Angiomotin prevents pluripotent lineage differentiation in mouse embryos via Hippo pathway-dependent and -independent mechanisms[J]. Nature Communications, 2013, 4
[146] HIRATE Y, HIRAHARA S, INOUE K, et al. Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos[J]. Curr Biol, 2013, 23(13): 1181-1194.
[147] HIRATE Y, SASAKI H. The role of angiomotin phosphorylation in the Hippo pathway during preimplantation mouse development[J]. Tissue Barriers, 2014, 2(1): e28127.
[148] WANG J, WANG L, FENG G, et al. Asymmetric Expression of LincGET Biases Cell Fate in Two-Cell Mouse Embryos[J]. Cell, 2018, 175(7): 1887-1901 e1818.
[149] WANG Y, ZHENG X, CHENG R, et al. Asymmetric expression of maternal mRNA governs first cell-fate decision[J]. FASEB J, 2021, 35(11): e22006.
[150] SOTERO-CAIO C G, PLATT R N, 2ND, SUH A, et al. Evolution and Diversity of Transposable Elements in Vertebrate Genomes[J]. Genome Biol Evol, 2017, 9(1): 161-177.
[151] MODZELEWSKI A J, SHAO W, CHEN J, et al. A mouse-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for development[J]. Cell, 2021, 184(22): 5541-5558 e5522.
[152] SAKASHITA A, KITANO T, ISHIZU H, et al. Transcription of MERVL retrotransposons is required for preimplantation embryo development[J]. Nature Genetics, 2023, 55(3): 484-+.
[153] YANG J, COOK L, CHEN Z. Systematic Perturbation of Thousands of Retroviral LTRs in Mouse Embryos[J]. bioRxiv, 2023
[154] XU R, LI S, WU Q, et al. Stage-specific H3K9me3 occupancy ensures retrotransposon silencing in human pre-implantation embryos[J]. Cell Stem Cell, 2022, 29(7): 1051-1066 e1058.
[155] CHANG N C, ROVIRA Q, WELLS J, et al. Zebrafish transposable elements show extensive diversification in age, genomic distribution, and developmental expression[J]. Genome Res, 2022, 32(7): 1408-1423.
[156] HENDRICKSON P G, DORAIS J A, GROW E J, et al. Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons[J]. Nature Genetics, 2017, 49(6): 925-934.
[157] SAVARESE F, DAVILA A, NECHANITZKY R, et al. Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression[J]. Genes & Development, 2009, 23(22): 2625-2638.
[158] WITTNER M, HAMPERL S, STOCKL U, et al. Establishment and Maintenance of Alternative Chromatin States at a Multicopy Gene Locus[J]. Cell, 2011, 145(4): 543-554.
[159] STEWART-MORGAN K R, REVERON-GOMEZ N, GROTH A. Transcription Restart Establishes Chromatin Accessibility after DNA Replication (vol 75, pg 284, 2019)[J]. Molecular Cell, 2019, 75(2): 408-414.
[160] JIANG Y P, HUANG J, LUN K H, et al. Genome-wide analyses of chromatin interactions after the loss of Pol I, Pol II, and Pol III[J]. Genome Biology, 2020, 21(1)
[161] SONG L, CRAWFORD G E. DNase-seq: a high-resolution technique for mapping active gene regulatory elements across the genome from mammalian cells[J]. Cold Spring Harb Protoc, 2010, 2010(2): pdb prot5384.
[162] SABO P J, KUEHN M S, THURMAN R, et al. Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays[J]. Nature Methods, 2006, 3(7): 511-518.
[163] BUENROSTRO J D, GIRESI P G, ZABA L C, et al. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position[J]. Nature Methods, 2013, 10(12): 1213-+.
[164] ALLAN J, FRASER R M, OWEN-HUGHES T, et al. Micrococcal nuclease does not substantially bias nucleosome mapping[J]. J Mol Biol, 2012, 417(3): 152-164.
[165] BUENROSTRO J D, WU B, LITZENBURGER U M, et al. Single-cell chromatin accessibility reveals principles of regulatory variation[J]. Nature, 2015, 523(7561): 486-490.
[166] SATPATHY A T, GRANJA J M, YOST K E, et al. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion[J]. Nat Biotechnol, 2019, 37(8): 925-936.
[167] CUSANOVICH D A, DAZA R, ADEY A, et al. Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing[J]. Science, 2015, 348(6237): 910-914.
[168] CHEN X, LITZENBURGER U M, WEI Y, et al. Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity[J]. Nat Commun, 2018, 9(1): 4590.
[169] RUBIN A J, PARKER K R, SATPATHY A T, et al. Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks[J]. Cell, 2019, 176(1-2): 361-376 e317.
[170] BAEK S, LEE I. Single-cell ATAC sequencing analysis: From data preprocessing to hypothesis generation[J]. Comput Struct Biotechnol J, 2020, 18: 1429-1439.
[171] WAGNER D E, WEINREB C, COLLINS Z M, et al. Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo[J]. Science, 2018, 360(6392): 981-987.
[172] SUR A, WANG Y, CAPAR P, et al. Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development[J]. Dev Cell, 2023, 58(24): 3028-3047 e3012.
[173] LIU C, LI R, LI Y, et al. Spatiotemporal mapping of gene expression landscapes and developmental trajectories during zebrafish embryogenesis[J]. Developmental Cell, 2022, 57(10): 1284-1298.e1285.
[174] SINGLEMAN C, HOLTZMAN N G. Growth and maturation in the zebrafish, Danio rerio: a staging tool for teaching and research[J]. Zebrafish, 2014, 11(4): 396-406.
[175] ILLUMINA. bcl2fastq[J]. bcl2fastq (RRID:SCR_015058), 2024
[176] CHEN S, ZHOU Y, CHEN Y, et al. fastp: an ultra-fast all-in-one FASTQ preprocessor[J]. Bioinformatics, 2018, 34(17): i884-i890.
[177] KIM D, PAGGI J M, PARK C, et al. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype[J]. Nat Biotechnol, 2019, 37(8): 907-915.
[178] LI H, HANDSAKER B, WYSOKER A, et al. The Sequence Alignment/Map format and SAMtools[J]. Bioinformatics, 2009, 25(16): 2078-2079.
[179] QUINLAN A R, HALL I M. BEDTools: a flexible suite of utilities for comparing genomic features[J]. Bioinformatics, 2010, 26(6): 841-842.
[180] RAMIREZ F, DUNDAR F, DIEHL S, et al. deepTools: a flexible platform for exploring deep-sequencing data[J]. Nucleic Acids Res, 2014, 42(Web Server issue): W187-191.
[181] INSTITUTE B. Picard Toolkit[J]. 2019
[182] ZHANG Y, LIU T, MEYER C A, et al. Model-based analysis of ChIP-Seq (MACS)[J]. Genome Biol, 2008, 9(9): R137.
[183] MCLEAN C Y, BRISTOR D, HILLER M, et al. GREAT improves functional interpretation of cis-regulatory regions[J]. Nat Biotechnol, 2010, 28(5): 495-501.
[184] HEINZ S, BENNER C, SPANN N, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities[J]. Mol Cell, 2010, 38(4): 576-589.
[185] KOSTER J, RAHMANN S. Snakemake--a scalable bioinformatics workflow engine[J]. Bioinformatics, 2012, 28(19): 2520-2522.
[186] HARRIS C R, MILLMAN K J, VAN DER WALT S J, et al. Array programming with NumPy[J]. Nature, 2020, 585(7825): 357-362.
[187] THE PANDAS DEVELOPMENT T. pandas-dev/pandas: Pandas[Z]. Zenodo. 2020.10.5281/zenodo.3509134
[188] VIRTANEN P, GOMMERS R, OLIPHANT T E, et al. SciPy 1.0: Fundamental Algorithms for Scientific Computing in Python[J]. Nature Methods, 2020, 17: 261-272.
[189] LI H. Tabix: fast retrieval of sequence features from generic TAB-delimited files[J]. Bioinformatics, 2011, 27(5): 718-719.
[190] THORVALDSDOTTIR H, ROBINSON J T, MESIROV J P. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration[J]. Brief Bioinform, 2013, 14(2): 178-192.
[191] PEDREGOSA F, VAROQUAUX G, GRAMFORT A, et al. Scikit-learn: Machine Learning in Python[J]. Journal of Machine Learning Research, 2011, 12: 2825-2830.
[192] WOLF F A, ANGERER P, THEIS F J. SCANPY: large-scale single-cell gene expression data analysis[J]. Genome Biol, 2018, 19(1): 15.
[193] TEAM R C. R: A language and environment for statistical computing[J]. MSOR connections, 2014, 1
[194] KENT W J, SUGNET C W, FUREY T S, et al. The human genome browser at UCSC[J]. Genome Research, 2002, 12(6): 996-1006.
[195] WHITE R J, COLLINS J E, SEALY I M, et al. A high-resolution mRNA expression time course of embryonic development in zebrafish[J]. Elife, 2017, 6
[196] NEPAL C, HADZHIEV Y, PREVITI C, et al. Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis[J]. Genome Research, 2013, 23(11): 1938-1950.
[197] BOGDANOVIC O, FERNANDEZ-MINAN A, TENA J J, et al. Dynamics of enhancer chromatin signatures mark the transition from pluripotency to cell specification during embryogenesis[J]. Genome Res, 2012, 22(10): 2043-2053.
[198] ROSS S E, VAZQUEZ-MARIN J, GERT K R B, et al. Evolutionary conservation of embryonic DNA methylome remodelling in distantly related teleost species[J]. Nucleic Acids Res, 2023, 51(18): 9658-9671.
[199] CASTRO-MONDRAGON J A, RIUDAVETS-PUIG R, RAULUSEVICIUTE I, et al. JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles[J]. Nucleic Acids Res, 2022, 50(D1): D165-D173.
[200] STUART T, SRIVASTAVA A, MADAD S, et al. Single-cell chromatin state analysis with Signac[J]. Nature Methods, 2021, 18(11): 1333-1341.
[201] BECHT E, MCINNES L, HEALY J, et al. Dimensionality reduction for visualizing single-cell data using UMAP[J]. Nat Biotechnol, 2018
[202] POLANSKI K, YOUNG M D, MIAO Z, et al. BBKNN: fast batch alignment of single cell transcriptomes[J]. Bioinformatics, 2020, 36(3): 964-965.
[203] YU G, WANG L G, HE Q Y. ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization[J]. Bioinformatics, 2015, 31(14): 2382-2383.
[204] LAWRENCE M, HUBER W, PAGES H, et al. Software for computing and annotating genomic ranges[J]. PLoS Comput Biol, 2013, 9(8): e1003118.
[205] ZHU L J, GAZIN C, LAWSON N D, et al. ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data[J]. BMC Bioinformatics, 2010, 11: 237.
[206] SCHEP A N, WU B, BUENROSTRO J D, et al. chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data[J]. Nature Methods, 2017, 14(10): 975-978.
[207] YU G C, WANG L G, HAN Y Y, et al. clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters[J]. Omics-a Journal of Integrative Biology, 2012, 16(5): 284-287.
[208] PLINER H A, PACKER J S, MCFALINE-FIGUEROA J L, et al. Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data[J]. Mol Cell, 2018, 71(5): 858-871 e858.
[209] HAGHVERDI L, BUTTNER M, WOLF F A, et al. Diffusion pseudotime robustly reconstructs lineage branching[J]. Nature Methods, 2016, 13(10): 845-848.
[210] YEE T W. Vector Generalized Linear and Additive Models: With an Implementation in R[J]. Springers New York, 2015
[211] LIU G, WANG W, HU S, et al. Inherited DNA methylation primes the establishment of accessible chromatin during genome activation[J]. Genome Res, 2018, 28(7): 998-1007.
[212] LIN X, YANG X, CHEN C, et al. Single-nucleus chromatin landscapes during zebrafish early embryogenesis[J]. Sci Data, 2023, 10(1): 464.
[213] BHAT P, CABRERA-QUIO L E, HERZOG V A, et al. SLAMseq resolves the kinetics of maternal and zygotic gene expression during early zebrafish embryogenesis[J]. Cell Rep, 2023, 42(2): 112070.
[214] GÖGELEIN H, HÜBY A. Interaction of saponin and digitonin with black lipid membranes and lipid monolayers[J]. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1984, 773(1): 32-38.
[215] BROUDE N E, BUDOWSKY E I. The reaction of glyoxal with nucleic acid components. 3. Kinetics of the reaction with monomers[J]. Biochim Biophys Acta, 1971, 254(3): 380-388.
[216] CHANNATHODIYIL P, HOUSELEY J. Glyoxal fixation facilitates transcriptome analysis after antigen staining and cell sorting by flow cytometry[J]. PLoS One, 2021, 16(1): e0240769.
[217] RICHTER K N, REVELO N H, SEITZ K J, et al. Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy[J]. Embo j, 2018, 37(1): 139-159.
[218] BAGERITZ J, KRAUSSE N, YOUSEFIAN S, et al. Glyoxal as an alternative fixative for single-cell RNA sequencing[J]. G3 (Bethesda), 2023, 13(10)
[219] LISCOVITCH-BRAUER N, MONTALBANO A, DENG J, et al. Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens[J]. Nat Biotechnol, 2021
[220] CHEN X, MIRAGAIA R J, NATARAJAN K N, et al. A rapid and robust method for single cell chromatin accessibility profiling[J]. Nat Commun, 2018, 9(1): 5345.
[221] XU W, WEN Y, LIANG Y, et al. A plate-based single-cell ATAC-seq workflow for fast and robust profiling of chromatin accessibility[J]. Nat Protoc, 2021, 16(8): 4084-4107.
[222] STAPEL L C, ZECHNER C, VASTENHOUW N L. Uniform gene expression in embryos is achieved by temporal averaging of transcription noise[J]. Genes Dev, 2017, 31(16): 1635-1640.
[223] LEE D D, SEUNG H S. Learning the parts of objects by non-negative matrix factorization[J]. Nature, 1999, 401(6755): 788-791.
[224] CHEN L, XU W, LIU K, et al. 5' Half of specific tRNAs feeds back to promote corresponding tRNA gene transcription in vertebrate embryos[J]. Sci Adv, 2021, 7(47): eabh0494.
[225] DUBIN M, FUCHS J, GRAF R, et al. Dynamics of a novel centromeric histone variant CenH3 reveals the evolutionary ancestral timing of centromere biogenesis[J]. Nucleic Acids Res, 2010, 38(21): 7526-7537.
[226] HABERLE V, LI N, HADZHIEV Y, et al. Two independent transcription initiation codes overlap on vertebrate core promoters[J]. Nature, 2014, 507(7492): 381-+.
[227] TAKESONO A, MOGER J, FAROOQ S, et al. Solute carrier family 3 member 2 (Slc3a2) controls yolk syncytial layer (YSL) formation by regulating microtubule networks in the zebrafish embryo[J]. Proc Natl Acad Sci U S A, 2012, 109(9): 3371-3376.
[228] BERGER M F, BADIS G, GEHRKE A R, et al. Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences[J]. Cell, 2008, 133(7): 1266-1276.
[229] HUME M A, BARRERA L A, GISSELBRECHT S S, et al. UniPROBE, update 2015: new tools and content for the online database of protein-binding microarray data on protein-DNA interactions[J]. Nucleic Acids Res, 2015, 43(Database issue): D117-122.
[230] YAMANAKA Y, MIZUNO T, SASAI Y, et al. A novel homeobox gene, can induce the organizer in a non-cell-autonomous manner[J]. Genes & Development, 1998, 12(15): 2345-2353.
[231] CARVALHO L, HEISENBERG C P. The yolk syncytial layer in early zebrafish development[J]. Trends Cell Biol, 2010, 20(10): 586-592.
[232] WEIRAUCH M T, YANG A, ALBU M, et al. Determination and inference of eukaryotic transcription factor sequence specificity[J]. Cell, 2014, 158(6): 1431-1443.
[233] NOYES M B, CHRISTENSEN R G, WAKABAYASHI A, et al. Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites[J]. Cell, 2008, 133(7): 1277-1289.
[234] LIBERZON A, RIDNER G, WALKER M D. Role of intrinsic DNA binding specificity in defining target genes of the mammalian transcription factor PDX1[J]. Nucleic Acids Res, 2004, 32(1): 54-64.
[235] SUN J, HE N, NIU L, et al. Global Quantitative Mapping of Enhancers in Rice by STARR-seq[J]. Genomics Proteomics Bioinformatics, 2019, 17(2): 140-153.