PXD063475

PXD063475 is an original dataset announced via ProteomeXchange.

Title	Multi-Omics Elucidation of KDM5C, KDM6A, and KMT2B Roles in Cancer Epigenetic Dysregulation and Transcriptional Reprogramming
Description	Histone-modifying enzymes (HMEs) are critical regulators of tumorigenesis through epigenetic reprogramming. While mutations in HMEs are recognized drivers of cancer epigenome dysregulation, systematic comparative analyses of their mutational impacts and functional divergence across malignancies remain underexplored. This study addresses this gap by investigating three HMEs—KDM5C (H3K4me3 demethylase), KMT2B (H3K4me3 methyltransferase), and KDM6A (H3K27me3 demethylase)—frequently mutated in diverse cancers. Using CRISPR/Cas9 knockout cell lines, we performed integrated multi-omics profiling encompassing genome-wide chromatin accessibility, transcriptomics, and chromatin-bound proteomics. Contrary to expectations that KMT2B loss (H3K4me3 depletion) and KDM5C loss (H3K4me3 accumulation) would induce opposing transcriptional programs, or that KDM6A deficiency (H3K27me3 accumulation) would exhibit distinct regulatory effects, our analyses revealed striking discrepancies between transcriptional outputs and chromatin-associated proteomic states across all three knockouts. Notably, each HME knockout elicited distinct transcriptional regulatory patterns, challenging conventional assumptions about their antagonistic or synergistic functions. These findings highlight context-dependent functional hierarchies among HMEs and underscore the necessity of multi-dimensional profiling to resolve epigenetic regulatory complexity. Our work advances the mechanistic understanding of cancer epigenetics and provides a framework for elucidating tumorigenic vulnerabilities linked to HME dysregulation.
HostingRepository	iProX
AnnounceDate	2025-04-29
AnnouncementXML	Submission_2025-11-06_23:38:07.256.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tengjiao Li
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-30 00:14:11	ID requested
⏵ 1	2025-11-06 23:38:07	announced

Dataset with its publication pending

submitter keyword: chromatin-bound proteomics

Lin Li
contact affiliation	Shanghai Jiao Tong University
contact email	linli.sjtu@sjtu.edu.cn
lab head
Tengjiao Li
contact affiliation	Shanghai Jiao Tong University
contact email	995262663@qq.com
dataset submitter

iProX dataset URI