PXD015173

PXD015173 is an original dataset announced via ProteomeXchange.

Title	Cdk1 controls global epigenetic landscape in embryonic stem cells
Description	The cyclin-dependent kinase 1 (Cdk1) represents an ancient cell cycle kinase that has been conserved from yeast to humans. Cdk1 is the only essential mammalian Cdk, which drives cytokinesis by phosphorylating a large number of cellular proteins. To uncover additional functions of Cdk1, we generated a knock-in strain of mice expressing an analog-sensitive version of Cdk1 in place of wild-type Cdk1. These mice and cells derived from them allow us to investigate Cdk1 function in essentially any compartment and at any stage of development. In our study, we focused on embryonic stem (ES) cells, as this cell type expresses particularly high levels of Cdk1. Very unexpectedly, we found that in ES cells the majority of Cdk1 substrates are localized on chromatin. Cdk1 phosphorylates a large number of proteins involved in epigenetic regulation, including writers and erasers of all major histone marks. Consistent with this finding, inhibition of Cdk1 altered histone modification status of ES cells. High levels of Cdk1 in ES cells (and in induced pluripotent stem cells) phosphorylate and partially inactivate Dot1l, the histone H3 lysine 79 methyltransferase responsible for placing activating H3K79 marks on gene bodies. Decrease of Cdk1 activity during ES cell differentiation de-represses Dot1l, thereby allowing coordinated expression of differentiation genes. These analyses indicate that Cdk1 functions to maintain the epigenetic identity of ES cells.
HostingRepository	PRIDE
AnnounceDate	2020-10-05
AnnouncementXML	Submission_2020-10-05_00:21:18.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joel Chick
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-27 06:14:11	ID requested
⏵ 1	2020-10-05 00:21:19	announced

Michowski W, Chick JM, Chu C, Kolodziejczyk A, Wang Y, Suski JM, Abraham B, Anders L, Day D, Dunkl LM, Li Cheong Man M, Zhang T, Laphanuwat P, Bacon NA, Liu L, Fassl A, Sharma S, Otto T, Jecrois E, Han R, Sweeney KE, Marro S, Wernig M, Geng Y, Moses A, Li C, Gygi SP, Young RA, Sicinski P, Cdk1 Controls Global Epigenetic Landscape in Embryonic Stem Cells. Mol Cell, 78(3):459-476.e13(2020) [pubmed]

curator keyword: Biological

submitter keyword: Proteomics, CDK1, kinase, analogue sensivtive

Peter Sicinski
contact affiliation	dana farber cancer institute and harvard medical school
contact email	Peter_Sicinski@dfci.harvard.edu
lab head
Joel Chick
contact affiliation	Harvard Medical School
contact email	chick.joel@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/10/PXD015173

PRIDE project URI

• PRIDE
  1. PXD015173
     1. Label: PRIDE project
     2. Name: Cdk1 controls global epigenetic landscape in embryonic stem cells