PXD053032

PXD053032 is an original dataset announced via ProteomeXchange.

Title	Rapid degradation of Histone Deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription
Description	Histone Deacetylase 1 (HDAC1) removes acetyl groups from lysine residues on the core histones, balancing histone acetyltransferase (HAT) activity. Despite this apparent repressive function, suppression of HDAC activity causes both up and downregulation of gene expression. Here we exploit the degradation tag (dTAG) system to rapidly degrade HDAC1 in embryonic stem cells (ESCs) lacking the paralog, HDAC2. Unlike HDAC inhibitors that lack isoform specificity the dTAG system allowed specific HDAC1 targeting and completely removed HDAC1 100x faster than genetic knockouts. HDAC1 degradation caused rapid increases in histone acetylation, with H2BK5 and H2BK11 most sensitive. The majority of differentially expressed genes following 2 hours of HDAC1 degradation were upregulated (275 genes up vs 15 down) with increased proportions of downregulated genes at 6 (1153 up vs 443 down) and 24 hours (1146 up vs 967 down). Upregulated genes showed increased H2BK5ac and H3K27ac around their transcriptional start site (TSS). In contrast, decreased acetylation of super-enhancers (SEs) was linked to the most strongly downregulated genes, leading to a collapse of the core pluripotency-associated gene network. These findings suggest that HDAC1 plays a crucial role in regulating the ESC gene expression network by maintaining the correct acetylation levels at key genomic sites.
HostingRepository	PRIDE
AnnounceDate	2024-11-27
AnnouncementXML	Submission_2024-11-27_13:34:03.654.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Collins
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-12 02:30:22	ID requested
⏵ 1	2024-11-27 13:34:04	announced

10.1093/NAR/GKAE1223;

submitter keyword: HDAC1, Histone, Acetylation

Mark Collins
contact affiliation	School of Biosciences Firth Court, Western Bank University of Sheffield Sheffield, S10 2TN United Kingdom
contact email	mark.collins@sheffield.ac.uk
lab head
Mark Collins
contact affiliation	University of Sheffield
contact email	mark.collins@sheffield.ac.uk
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/2024/11/PXD053032

PRIDE project URI

• PRIDE
  1. PXD053032
     1. Label: PRIDE project
     2. Name: Rapid degradation of Histone Deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription