PXD057637-1

PXD057637 is an original dataset announced via ProteomeXchange.

Title	Analyses of an intellectual disability-associated allele in the chromatin modifier KDM5 reveals insulator activity in the brain
Description	KDM5 family proteins are best known for their demethylation of the promoter proximal chromatin mark H3K4me3. KDM5-regulated transcription is critical in the brain, with variants in the X-linked paralog KDM5C causing the intellectual disability (ID) disorder, Claes-Jensen syndrome. Although the demethylase activity of KDM5C is known to be important for neuronal function, the contribution of non-enzymatic activities remains less characterized. We therefore used Drosophila to model the ID variant Kdm5L854F that disrupts a C5HC2 zinc finger adjacent to the enzymatic JmjC domain. Kdm5L854F causes similar transcriptional changes in the brain to a demethylase dead strain, Kdm5JmjC*, despite having little effect on enzymatic activity. KDM5L854F is also distinct from KDM5JmjC* in its reduced interactions with insulator proteins and enhancement of position effect variegation. Instead, the common transcriptional deficits likely result from both the JmjC and C5HC2 domains driving proper genomic architecture, as both variants exhibited reduced looping linked to altered transcription.
HostingRepository	PRIDE
AnnounceDate	2026-08-03
AnnouncementXML	Submission_2026-08-03_11:40:19.306.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simone Sidoli
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: NEWT:7227;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-07 15:55:00	ID requested
⏵ 1	2026-08-03 11:40:19	announced

Dataset with its publication pending

submitter keyword: KDM5C, Genomic architecture, Transcription regulation, Zinc finger domain, Intellectual disability

Simone Sidoli
contact affiliation	Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 14061, United States
contact email	simone.sidoli@einsteinmed.edu
lab head
Simone Sidoli
contact affiliation	Albert Einstein College of Medicine
contact email	simone.sidoli@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057637
     1. Label: PRIDE project
     2. Name: Analyses of an intellectual disability-associated allele in the chromatin modifier KDM5 reveals insulator activity in the brain