An alternative CTCF isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis

Li, Jiao1,2,3,4; Huang, Kaimeng1,2,3; Hu, Gongcheng1,2,3,4; Babarinde, Isaac A.5; Li, Yaoyi1,2,3,4; Dong, Xiaotao1,2,3,4; Chen, Yu-Sheng6; Shang, Liping1; Guo, Wenjing1; Wang, Junwei1; Chen, Zhaoming1,2; Hutchins, Andrew P.5; Yang, Yun-Gui4,6; Yao, Hongjie1,2,3,4

2019-04-04

10.1038/s41467-019-08949-w

Nature Communications   影响因子和分区

2041-1723

CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s). Functionally, we find that CTCF-s competes with the genome binding of canonical CTCF and binds a similar DNA sequence. CTCF-s binding disrupts CTCF/cohesin binding, alters CTCF-mediated chromatin looping and promotes the activation of IFI6 that leads to apoptosis. This effect is caused by an abnormal long-range interaction at the IFI6 enhancer and promoter. Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression.

SCI

英语

NI期刊

其他

Guangdong Provincial Key Laboratory of Biocomputing[2016B030301007]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000463313200011

NATURE PUBLISHING GROUP

Web of Science

1.Guangzhou Med Univ, Chinese Acad Sci, CAS Key Lab Regenerat Biol,Guangzhou Inst Biomed, Hefei Inst Stem Cell & Regenerat Med,Joint Sch Li, Guangzhou 510530, Guangdong, Peoples R China
2.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangdong Prov Key Lab Biocomp,Guangzhou Regenera, Guangzhou 510530, Guangdong, Peoples R China
3.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Peoples R China
6.Chinese Acad Sci, Beijing Inst Genom, Key Lab Genom & Precis Med, Beijing 100101, Peoples R China

Li, Jiao,Huang, Kaimeng,Hu, Gongcheng,et al. An alternative CTCF isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis[J]. Nature Communications,2019,10.

Li, Jiao.,Huang, Kaimeng.,Hu, Gongcheng.,Babarinde, Isaac A..,Li, Yaoyi.,...&Yao, Hongjie.(2019).An alternative CTCF isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis.Nature Communications,10.

Li, Jiao,et al."An alternative CTCF isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis".Nature Communications 10(2019).