PXD048969

PXD048969 is an original dataset announced via ProteomeXchange.

Title	Extensive folding variability between homologous chromosomes in mammalian cells
Description	Genetic variation and 3D chromatin structure have major roles in gene regulation. Structural differences between genotypically different chromosomes and their effects on gene expression remain ill understood, due to challenges in mapping 3D genome structure with allele-specific resolution. Here, we applied Genome Architecture Mapping (GAM) to a hybrid mouse embryonic stem cell (ESC) line with high SNP density. Given the high efficiency of GAM in haplotype phasing, we could resolve allele-specific 3D genome structures with high sensitivity. We discovered extensive genotype-specific folding of chromosomes in compartments, topologically associating domains (TADs), long-range enhancer-promoter contacts and CTCF loops, often coinciding with allele-specific gene expression in association with Polycomb repression. We show that histone genes are expressed with allelic imbalance in ESCs, and involved in allele-specific chromatin contacts marked by H3K27me3. Functional analysis through conditional Ezh2- or Ring1b-knockdown shows a role for Polycomb repression in tuning histone protein levels. Our work reveals that the homologous chromosomes have highly distinct 3D folding structures, and their intricate relationships with gene-specific mechanisms of allelic expression imbalance.
HostingRepository	PRIDE
AnnounceDate	2025-01-30
AnnouncementXML	Submission_2025-01-30_07:37:24.081.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guido Mastrobuoni
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-29 05:25:20	ID requested
⏵ 1	2025-01-30 07:37:24	announced

Dataset with its publication pending

submitter keyword: LC-MSMS, Genome Architecture Mapping (GAM),chromatin, Polycomb

Stefan Kempa
contact affiliation	Quantitative Proteomics and Metabolomics Berlin Institute for Medical Systems Biology (BIMSB) Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft Hannoversche Straße 28 10115 Berlin
contact email	stefan.kempa@mdc-berlin.de
lab head
Guido Mastrobuoni
contact affiliation	Berlin Institute for Medical Systems Biology at the Max Delbrueck Centrum for Molecular Medicine
contact email	guido.mastrobuoni@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048969
     1. Label: PRIDE project
     2. Name: Extensive folding variability between homologous chromosomes in mammalian cells