PXD025053-1

PXD025053 is an original dataset announced via ProteomeXchange.

Title	ChIP-MS of HP1-beta (CBX1) and ubiquitylome of KAP1 (TRIM28) in mESCs
Description	Heterochromatin binding protein HP1β plays an important role in chromatin organization and cell differentiation, however the underlying mechanisms remain unclear. Here, we generated HP1β-/- embryonic stem cells and observed reduced heterochromatin clustering and impaired differentiation. We found that during stem cell differentiation, HP1β is phosphorylated at serine 89 by CK2, which creates a binding site for the pluripotency regulator KAP1. This phosphorylation dependent sequestration of KAP1 in heterochromatin compartments causes a downregulation of pluripotency factors and triggers pluripotency exit. Accordingly, HP1β-/- and phospho-mutant cells exhibited impaired differentiation, while ubiquitination-deficient KAP1ΔRing cells had the opposite phenotype with enhanced differentiation. These results suggest that KAP1 regulates pluripotency via its ubiquitination activity. We propose that the formation of subnuclear membraneless heterochromatin compartments may serve as a dynamic reservoir to trap or release cellular factors. The sequestration of essential regulators defines a novel and active role of heterochromatin in gene regulation and represents a dynamic mode of remote control to regulate cellular processes like cell fate decisions.
HostingRepository	PRIDE
AnnounceDate	2021-09-24
AnnouncementXML	Submission_2021-09-24_01:34:42.419.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Enes Ugur
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitination signature dipeptidyl lysine; monohydroxylated residue; iodoacetic acid derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-29 02:45:02	ID requested
⏵ 1	2021-09-24 01:34:42	announced
2	2021-09-24 02:45:06	announced	2021-09-24: Updated project metadata.

10.1093/NAR/GKAB548;

submitter keyword: Phase separation, pluripotency exit, chromatin structure, heterochromatin, chromocenter

Heinrich Leonhardt
contact affiliation	Department of Humanbiology & BioImaging, Faculty of Biology, Ludwig-Maximilians-Universität München
contact email	h.leonhardt@lmu.de
lab head
Enes Ugur
contact affiliation	Heinrich Leonhardt Lab, Department of Humanbiology & BioImaging, LMU Munich
contact email	ugur@bio.lmu.de
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/2021/09/PXD025053

PRIDE project URI

• PRIDE
  1. PXD025053
     1. Label: PRIDE project
     2. Name: ChIP-MS of HP1-beta (CBX1) and ubiquitylome of KAP1 (TRIM28) in mESCs