PXD031767

PXD031767 is an original dataset announced via ProteomeXchange.

Title	Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia
Description	Schizophrenia (SZ) is a psychiatric disorder with complex genetic risk dictated by interactions between hundreds of risk variants. Epigenetic factors, such as histone posttranslational modifications (PTMs), have been shown to play critical roles in many neurodevelopmental processes, and when perturbed may also contribute to the precipitation of disease. Here, we apply an unbiased proteomics approach to evaluate combinatorial histone PTMs in human induced pluripotent stem cell (hiPSC)-derived forebrain neurons from individuals with SZ. We observe hyper-acetylation of H2A.Z and H4 in neurons derived from SZ cases, results that were confirmed in postmortem human brain. We demonstrate that the bromodomain and extraterminal (BET) protein, BRD4, is a bona fide ‘reader’ of H2A.Z acetylation, and further provide evidence that BET family protein inhibition ameliorates transcriptional abnormalities in patient-derived neurons. Thus, treatments aimed at alleviating BET protein interactions with hyperacetylated histones may aid in the prevention or treatment of SZ.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:54.303.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natarajan Bhanu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; acetylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-21 02:40:43	ID requested
1	2022-05-06 12:19:50	announced
⏵ 2	2023-11-14 08:55:54	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: BET proteins, Mass Spectrometry, Histone modifications,Schizophrenia, RNA-seq

Benjamin A Garcia
contact affiliation	Raymond H. Wittcoff Distinguished Professor and Head Department of Biochemistry and Molecular Biophysics Washington University School of Medicine St. Louis, MO 63110
contact email	bagarcia@wustl.edu
lab head
Natarajan Bhanu
contact affiliation	Washington University
contact email	bhanujayavel@hotmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031767
     1. Label: PRIDE project
     2. Name: Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BET family proteins in schizophrenia