| Literature DB >> 32240602 |
Wojciech Michowski1, Joel M Chick2, Chen Chu3, Aleksandra Kolodziejczyk3, Yichen Wang4, Jan M Suski3, Brian Abraham5, Lars Anders5, Daniel Day5, Lukas M Dunkl3, Mitchell Li Cheong Man6, Tian Zhang2, Phatthamon Laphanuwat3, Nickolas A Bacon3, Lijun Liu3, Anne Fassl3, Samanta Sharma3, Tobias Otto3, Emanuelle Jecrois3, Richard Han3, Katharine E Sweeney3, Samuele Marro7, Marius Wernig7, Yan Geng3, Alan Moses8, Cheng Li4, Steven P Gygi2, Richard A Young5, Piotr Sicinski9.
Abstract
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.Entities:
Keywords: analog sensitive kinase; cell cycle; cyclin; cyclin dependent kinase; differentiation; embryonic stem cells; epigenetics; phosphoproteomics
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Year: 2020 PMID： 32240602 PMCID： PMC7214218 DOI： 10.1016/j.molcel.2020.03.010
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970