PXD001660

PXD001660 is an original dataset announced via ProteomeXchange.

Title	Histone deacetylase inhibitors cause the selective depletion of bromodomain containing proteins
Description	Histone deacetylases (HDACs) and acetyltransferases control the epigenetic regulation of gene expression through modification of histone marks. Histone deacetylase inhibitors (HDACi) are small molecules that interfere with histone tail modification thus altering chromatin structure and epigenetically controlled pathways. They promote apoptosis in proliferating cells and are promising anti-cancer drugs. While some HDACis have already been approved for therapy and others are in different phases of clinical trials, the exact mechanism of action of this drug class remains elusive. Previous studies have shown that HDACis cause massive changes in chromatin structure but only moderate changes in gene expression. To which extent these changes manifest at the protein level has never been investigated on a proteome-wide scale. Here, we have studied HDACi-treated cells by large-scale mass spectrometry based proteomics. We show that HDACi treatment affects primarily the nuclear proteome and induces a selective decrease of bromodomain containing proteins (BCPs), the main readers of acetylated histone marks. By combining time-resolved proteome and transcriptome profiling, we show that BCPs are affected at the protein level as early as 12 hours after HDACi treatment and that their abundance is regulated by a combination of transcriptional and post-transcriptional mechanisms. Using gene silencing, we demonstrate that the decreased abundance of BCPs is sufficient to mediate important transcriptional changes induced by HDACi. Our data reveals a new aspect of the mechanism of action of HDACi that is mediated by an interplay between histone acetylation and the abundance of BCPs.
HostingRepository	PRIDE
AnnounceDate	2017-10-24
AnnouncementXML	Submission_2017-10-24_00:16:54.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alessandro Ori
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-01-08 02:28:32	ID requested
1	2015-03-18 07:36:12	announced
2	2017-06-20 05:43:07	announced	Updated project metadata.
⏵ 3	2017-10-24 00:16:55	announced	Updated project metadata.

Mackmull MT, Iskar M, Parca L, Singer S, Bork P, Ori A, Beck M, Histone Deacetylase Inhibitors (HDACi) Cause the Selective Depletion of Bromodomain Containing Proteins (BCPs). Mol Cell Proteomics, 14(5):1350-60(2015) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: HDACi, LC-MS/MS, bromodomain, gene expression, nucleus

Martin Beck
contact affiliation	Structural and Computational Biology Unit European Molecular Biology Laboratory Meyerhofstr. 1 69117 Heidelberg Germany
contact email	martin.beck@embl.de
lab head
Alessandro Ori
contact affiliation	EMBL
contact email	aleori@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001660
     1. Label: PRIDE project
     2. Name: Histone deacetylase inhibitors cause the selective depletion of bromodomain containing proteins