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Extensive folding variability between homologous chromosomes in mammalian cells [GAM]

ABSTRACT: Extensive folding variability between homologous chromosomes in mammalian cells [GAM]

PROVIDER: PRJNA1071570 | ENA |

REPOSITORIES: ENA

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Extensive folding variability between homologous chromosomes in mammalian cells [GAM]

Project 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 its high efficiency of haplotype phasing, GAM resolves 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 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.

2025-01-29 | GSE254717 | GEO

Extensive folding variability between homologous chromosomes in mammalian cells

Project 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.

2025-01-30 | PXD048969 | Pride

Extensive folding variability between homologous chromosomes in mammalian cells [ChIP-Seq]

2025-01-29 | GSE254710 | GEO

Extensive folding variability between homologous chromosomes in mammalian cells [RNA-seq]

2025-01-29 | GSE254675 | GEO

Extensive folding variability between homologous chromosomes in mammalian cells

Project description:Extensive folding variability between homologous chromosomes in mammalian cells

| PRJNA1071571 | ENA

Extensive folding variability between homologous chromosomes in mammalian cells [RNA-seq]

Project description:Extensive folding variability between homologous chromosomes in mammalian cells [RNA-seq]

| PRJNA1071503 | ENA

Extensive folding variability between homologous chromosomes in mammalian cells [ChIP-Seq]

Project description:Extensive folding variability between homologous chromosomes in mammalian cells [ChIP-Seq]

| PRJNA1071563 | ENA

Extensive folding variability between homologous chromosomes in mammalian cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-01-29 | GSE254723 | GEO

Transcription profiling of human THP-1 cells wild type vs overexpressing GAM or siRNAs directed against GAM (siGAM) challenged by LPS

Project description:24 hours following transfection with either a control mix, a construct overexpressing GAM or siRNAs directed against GAM (siGAM), THP-1 cells were challenged with LPS 100 ng/ml. RNAs were analyzed after 6 hours of LPS challenge

2010-06-09 | E-TABM-868 | biostudies-arrayexpress

Multiplex GAM datasets collected with an average of three nuclear profiles each

Project description:Technologies for measuring 3D genome topology are increasingly important for studying mechanisms of gene regulation, for genome assembly and for mapping of genome rearrangements. We developed multiplex-GAM, a faster and more affordable version of Genome Architecture Mapping (GAM), a ligation-free technique to map chromatin contacts genome-wide. We applied multiplex-GAM to Mouse ES cells.

2022-06-13 | GSE166380 | GEO

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