H4K20me3 methyltransferase SUV420H2 shapes the chromatin landscape of pluripotent embryonic stem cells

Kurup, Jiji T.1,2; Han, Zhijun3; Jin, Wenfei3; Kidder, Benjamin L.1,2

2020-12-01

10.1242/dev.188516

DEVELOPMENT   影响因子和分区

0950-1991

1477-9129

Heterochromatin, a densely packed chromatin state that is transcriptionally slent, is a critical regulator of gene expression. However, it is unclear how the repressive histone modification H4K20me3 or the histone methyltransferase SUV420H2 regulates embryonic stem (ES) cell fate by patterning the epigenetic landscape. Here, we report that depletion of SUV420H2 leads to a near-complete loss of H4K20me3 genome wide, dysregulated gene expression and delayed ES cell differentiation. SUV420H2-bound regions are enriched with repetitive DNA elements, which are de-repressed in SUV420H2 knockout ES cells. Moreover, SUV420H2 regulation of H4K20me3-marked heterochromatin controls chromatin architecture, induding finescale chromatin interactions in pluripotent ES cells. Our results indicate that SUV420H2 plays a crucial role in stabilizing the three-dimensional chromatin landscape of ES cells, as loss of SUV420H2 resulted in A/B compartment switching, perturbed chromatin insulation, and altered chromatin interactions of pericentric heterochromatin and surrounding regions, indicative of localized decondensation. In addition, depletion of SUV420H2 resulted in compromised interactions between H4K20me3 and gene-regulatory regions. Together, these findings describe a new role for SUV420H2 in regulating the chromatin landscape of ES cells.

Embryonic stem cells 3D genome Chromatin architecture Pluripotent Epigenetics Chromatin ChIP-Seq SUV420H2 H4K20me3

SCI

英语

其他

National Heart, Lung, and Blood Institute[1K22HL126842-01A1]

Developmental Biology

Developmental Biology

WOS:000599460700002

COMPANY BIOLOGISTS LTD

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI 48201 USA
2.Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA
3.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Peoples R China

Kurup, Jiji T.,Han, Zhijun,Jin, Wenfei,et al. H4K20me3 methyltransferase SUV420H2 shapes the chromatin landscape of pluripotent embryonic stem cells[J]. DEVELOPMENT,2020,147(23).

Kurup, Jiji T.,Han, Zhijun,Jin, Wenfei,&Kidder, Benjamin L..(2020).H4K20me3 methyltransferase SUV420H2 shapes the chromatin landscape of pluripotent embryonic stem cells.DEVELOPMENT,147(23).

Kurup, Jiji T.,et al."H4K20me3 methyltransferase SUV420H2 shapes the chromatin landscape of pluripotent embryonic stem cells".DEVELOPMENT 147.23(2020).