PXD028824-1

PXD028824 is an original dataset announced via ProteomeXchange.

Title	DOT1L regulates pericentromeric heterochromatin
Description	Many repetitive DNA elements are packaged in heterochromatin, but depend on occasional transcription to maintain long-term silencing. The factors that promote transcription of repeat elements in heterochromatin are largely unknown. Here, we show that DOT1L, a histone methyltransferase that modifies lysine 79 of histone H3 (H3K79), is required for transcription of major satellite repeats to maintain pericentromeric heterochromatin (PCH), and that this function is essential for preimplantation development. DOT1L is a transcriptional activator at single-copy genes but does not have a known role in repeat element transcription. We show that H3K79me3 is specifically enriched at repetitive elements, that loss of DOT1L compromises pericentromeric major satellite transcription, and that this function depends on interaction between DOT1L and the chromatin remodeler SMARCA5. DOT1L inhibition causes chromosome breaks and cell cycle defects, and leads to embryonic lethality. Together, our findings uncover a vital new role for DOT1L in transcriptional activation of heterochromatic repeats.
HostingRepository	PRIDE
AnnounceDate	2023-05-26
AnnouncementXML	Submission_2023-05-26_08:32:05.939.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKietLam
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-29 00:11:27	ID requested
⏵ 1	2023-05-26 08:32:06	announced

Dataset with its publication pending

submitter keyword: mESCs, embryo, mass spectrometry,DOT1L, chromatin, pericentromere

TuKietLam
contact affiliation	Yale University Department of Molecular Biophysics and Biochemistry
contact email	tukiet.lam@yale.edu
lab head
TuKietLam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
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/2023/05/PXD028824

PRIDE project URI

• PRIDE
  1. PXD028824
     1. Label: PRIDE project
     2. Name: DOT1L regulates pericentromeric heterochromatin