PXD036471-1

PXD036471 is an original dataset announced via ProteomeXchange.

Title	Alternative Splicing of HDAC7 Regulates its Interaction with 14-3-3 Proteins to Alter Histone Marks and Target Gene Expression
Description	Epigenetics and Alternative Splicing are both critical mechanisms guiding gene expression. Several studies have demonstrated that epigenetic marks can influence alternative splicing decisions, but less is known about how alternative splicing may impact epigenetics. Here, we demonstrate that several genes encoding histone modifying enzymes are alternatively spliced downstream of T cell activation signaling pathways, including HDAC7, a gene previously implicated in controlling gene expression programs and differentiation in T cells. Using CRISPR-Cas9 gene editing and cDNA expression, we show that differential inclusion of HDAC7 exon 9 controls the interaction of HDAC7 with protein chaperones with resulting impact on histone modifications and gene expression. Notably, the long isoform, which is favored upon JNK signaling, promotes expression of several critical T cell surface proteins including CD3, CD28, CD69. Thus, we demonstrate that alternative splicing of HDAC7 has a global impact on epigenetics and gene expression, and may contribute to T cell regulation.
HostingRepository	PRIDE
AnnounceDate	2023-02-18
AnnouncementXML	Submission_2023-02-18_13:13:50.762.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	LauraAgosto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; acetylated residue; monohydroxylated residue; dimethylated residue; Trimethyl; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-02 06:28:04	ID requested
⏵ 1	2023-02-18 13:13:51	announced

Dataset with its publication pending

submitter keyword: nanoLC-MS/MS, CD28, CD69, Histone PTM, Apoptosis, Epigenetics,HDAC7

Kristen W.Lynch
contact affiliation	Department of Biochemistry and Biophysics, Genetics (Secondary), Perelman School of Medicine, Univerisity of Pennsylvania
contact email	klync@pennmedicine.upenn.edu
lab head
LauraAgosto
contact affiliation	University of Pennsylvania Perelman School of Medicine
contact email	lauag@pennmedicine.upenn.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036471
     1. Label: PRIDE project
     2. Name: Alternative Splicing of HDAC7 Regulates its Interaction with 14-3-3 Proteins to Alter Histone Marks and Target Gene Expression