Cdk1 Controls Global Epigenetic Landscape in Embryonic Stem Cells

被引：83

作者：

Michowski, Wojciech ^{[1
,2
,3
]}

Chick, Joel M. ^{[4
]}

Chu, Chen ^{[1
,2
]}

Kolodziejczyk, Aleksandra ^{[1
,2
]}

Wang, Yichen ^{[5
]}

Suski, Jan M. ^{[1
,2
]}

Abraham, Brian ^{[6
,7
]}

Anders, Lars ^{[6
,7
]}

Day, Daniel ^{[6
,7
]}

Dunkl, Lukas M. ^{[1
,2
]}

Man, Mitchell Li Cheong ^{[8
]}

Zhang, Tian ^{[4
]}

Laphanuwat, Phatthamon ^{[1
,2
]}

Bacon, Nickolas A. ^{[1
,2
]}

Liu, Lijun ^{[1
,2
]}

Fassl, Anne ^{[1
,2
]}

Sharma, Samanta ^{[1
,2
]}

Otto, Tobias ^{[1
,2
]}

Jecrois, Emanuelle ^{[1
,2
]}

Han, Richard ^{[1
,2
]}

Sweeney, Katharine E. ^{[1
,2
]}

Marro, Samuele ^{[9
,10
]}

Wernig, Marius ^{[9
,10
]}

Geng, Yan ^{[1
,2
]}

Moses, Alan ^{[8
,11
]}

Li, Cheng ^{[5
]}

Gygi, Steven P. ^{[4
]}

Young, Richard A. ^{[6
,7
]}

Sicinski, Piotr ^{[1
,2
]}

机构：

[1] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[2] Harvard Med Sch, Blavatn Inst, Dept Genet, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Dept Oncol Pathol, Boston, MA 02215 USA

[4] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA

[5] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China

[6] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[7] MIT, Dept Biol, Cambridge, MA 02142 USA

[8] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON M5S 3B2, Canada

[9] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Med Sch, Stanford, CA 94305 USA

[10] Stanford Univ, Dept Pathol, Med Sch, Stanford, CA 94305 USA

[11] Ctr Anal Genome Evolut & Funct, Toronto, ON M5S 3B2, Canada

来源：

MOLECULAR CELL | 2020年 / 78卷 / 03期

关键词：

UNNATURAL NUCLEOTIDE SPECIFICITY; CYCLE REGULATION; EXPRESSION ANALYSIS; WILD-TYPE; PHOSPHORYLATION; GENE; KINASE; PLURIPOTENT; METHYLATION; INHIBITOR;

D O I：

10.1016/j.molcel.2020.03.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The cyclin-dependent kinase 1 (Cdk1) drives cell division. To uncover additional functions of Cdk1, we generated knockin mice expressing an analog-sensitive version of Cdk1 in place of wild-type Cdk1. In our study, we focused on embryonic stem cells (ESCs), because this cell type displays particularly high Cdk1 activity. We found that in ESCs, a large fraction of Cdk1 substrates is localized on chromatin. Cdk1 phosphorylates many proteins involved in epigenetic regulation, including writers and erasers of all major histone marks. Consistent with these findings, inhibition of Cdk1 altered histone-modification status of ESCs. High levels of Cdk1 in ESCs phosphorylate and partially inactivate Dot1l, the H3K79 methyltransferase responsible for placing activating marks on gene bodies. Decrease of Cdk1 activity during ESC differentiation de-represses Dot1l, thereby allowing coordinated expression of differentiation genes. These analyses indicate that Cdk1 functions to maintain the epigenetic identity of ESCs.

引用

页码：459 / +

页数：31

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