Cdk1 Controls Global Epigenetic Landscape in Embryonic Stem Cells
Name
nihms-1578119.pdf
Description
Accepted version
Size
2.81 MB
Format
Adobe PDF
Checksum (MD5)
49da14016857be78cc50a7f40ef60ecc
Author(s)
Michowski, Wojciech
Chick, Joel M
Chu, Chen
Kolodziejczyk, Aleksandra
Wang, Yichen
Suski, Jan M
Abraham, Brian Joseph
Anders, Lars
Day, Daniel
Dunkl, Lukas M
Date Issued
2020
Journal
Molecular Cell
Publisher
Elsevier BV
Version
Author's final manuscript
Abstract
© 2020 Elsevier Inc. 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
10.1016/J.MOLCEL.2020.03.010
https://doi.org/10.1016/J.MOLCEL.2020.03.010
