PXD045644

PXD045644 is an original dataset announced via ProteomeXchange.

Title	Regulation of Histone Acetylation by SUMOylation Through TFAP2C Binding to the Chromatin and Recruitment of HDAC Complex
Description	Enhancers are fundamental to gene regulation. Post-translational modifications by the small ubiquitin-like modifiers (SUMO) modify chromatin regulation enzymes, including histone acetylases and deacetylases. However, it remains unclear whether SUMOylation regulates enhancer marks, acetylation at the 27th lysine residue of the histone H3 protein (H3K27Ac). We hypothesize that SUMOylation regulates H3K27Ac. To test this hypothesis, we performed genome-wide ChIP-seq analyses. We discovered that knockdown (KD) of the SUMO activating enzyme catalytic subunit UBA2 reduced H3K27Ac at most enhancers. Bioinformatic analysis revealed that TFAP2C-binding sites are enriched in enhancers whose H3K27Ac was reduced by UBA2 KD. ChIP-seq analysis in combination with molecular biological methods showed that TFAP2C binding to enhancers increased upon UBA2 KD or inhibition of SUMOylation by a small molecule SUMOylation inhibitor. However, this is not due to the SUMOylation of TFAP2C itself. Proteomics analysis of TFAP2C interactome on the chromatin identified histone deacetylation (HDAC) machinery. TFAP2C KD reduced HDAC binding to chromatin and increased H3K27Ac marks at enhancer regions, suggesting that TFAP2C is involved in recruiting HDAC. Taken together, our findings provide important insights into regulation of enhancer marks by SUMOylation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:35:58.587.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shih-Ting Huang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-25 04:02:55	ID requested
1	2024-04-12 20:14:48	announced
⏵ 2	2024-10-22 06:35:59	announced	2024-10-22: Updated project metadata.

10.21203/RS.3.RS-4201913/V1;

submitter keyword: Human, TFAP2C, Splicesome, Histone Deactylace, HDAC, Enhancer, Histone Modifications, LC-MS/MS

Yuan Chen
contact affiliation	Division of Surgical Sciences, Department of Surgery and Moores Cancer Center, Department of Chemistry and Biochemistry, UC San Diego and Department of Computational and Quantitative Medicine, Department of Molecular Medicine, Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Department of Computational and Quantitative Medicine, and Toni Stephenson Lymphoma Center Beckman Research Institute, City of Hope, Duarte, CA 91010
contact email	yuc020@ucsd.edu
lab head
Shih-Ting Huang
contact affiliation	University of California, San Diego
contact email	shh132@ucsd.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045644
     1. Label: PRIDE project
     2. Name: Regulation of Histone Acetylation by SUMOylation Through TFAP2C Binding to the Chromatin and Recruitment of HDAC Complex