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Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes [RNA-seq]

ABSTRACT: Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes [RNA-seq]

PROVIDER: PRJNA860200 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20314865_1.fastq.gz	Fastqsanger.gz
	SRR20314865_2.fastq.gz	Fastqsanger.gz
	SRR20314866_1.fastq.gz	Fastqsanger.gz
	SRR20314866_2.fastq.gz	Fastqsanger.gz
	SRR20314867_1.fastq.gz	Fastqsanger.gz

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Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes [RNA-seq]

Project description:To produce a diverse antibody repertoire, immunoglobulin heavy-chain (Igh) loci undergo large-scale alterations in structure to facilitate juxtaposition and recombination of spatially separated variable (VH), diversity (DH), and joining (JH) genes. These chromosomal alterations are poorly understood. Uncovering their patterns shows how chromosome dynamics underpins antibody diversity. Using tiled Capture Hi-C, we produce a comprehensive map of chromatin interactions throughout the 2.8-Mb Igh locus in progenitor B cells. We find that the Igh locus folds into semi-rigid subdomains and undergoes flexible looping of the VH genes to its 3′ end, reconciling two views of locus organization. Deconvolution of single Igh locus conformations using polymer simulations identifies thousands of different structures. This heterogeneity may underpin the diversity of V(D)J recombination events. All three immunoglobulin loci also participate in a highly specific, developmentally regulated network of interchromosomal interactions with genes encoding B cell-lineage factors. This suggests a model of interchromosomal coordination of B cell development.

2023-08-25 | GSE208601 | GEO

Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes [Hi-C]

2023-08-25 | GSE208600 | GEO

Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes

Project description:Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes

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Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes [Hi-C]

Project description:Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes [Hi-C]

| PRJNA860201 | ENA

Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes.

Project description:To produce a diverse antibody repertoire, immunoglobulin heavy-chain (Igh) loci undergo large-scale alterations in structure to facilitate juxtaposition and recombination of spatially separated variable (VH), diversity (DH), and joining (JH) genes. These chromosomal alterations are poorly understood. Uncovering their patterns shows how chromosome dynamics underpins antibody diversity. Using tiled Capture Hi-C, we produce a comprehensive map of chromatin interactions throughout the 2.8-Mb Igh locus in progenitor B cells. We find that the Igh locus folds into semi-rigid subdomains and undergoes flexible looping of the VH genes to its 3' end, reconciling two views of locus organization. Deconvolution of single Igh locus conformations using polymer simulations identifies thousands of different structures. This heterogeneity may underpin the diversity of V(D)J recombination events. All three immunoglobulin loci also participate in a highly specific, developmentally regulated network of interchromosomal interactions with genes encoding B cell-lineage factors. This suggests a model of interchromosomal coordination of B cell development.

| S-EPMC10548092 | biostudies-literature

Intra- and interchromosomal contact mapping reveals the Igh locus has extensive conformational heterogeneity and interacts with B-lineage genes

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

2023-08-25 | GSE208602 | GEO

A distinct motif for numerous CTCF binding sites in the murine IgH locus

Project description:Our studies have revealed that a large class of CTCF binding sites – namely the upstream sites – conform neither to a conformational nor a local recombinase activating role. Their conserved spatial distances upstream of V gene segments suggests a possible role in insulating V gene segments from neighboring V gene segments. In any case, understanding the sequence determinants of CTCF binding to the murine IgH locus should facilitate future studies evaluating how IgH locus accessibility regulates CTCF binding as well as the functions that CTCF plays in regulating the recombinational accessibility of VH gene segments during B cell development.

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Project description:Numerous B-cell lymphomas feature translocations linking oncogenes with the IgH locus and epigenetic drugs such as histone deacetylase inhibitors (HDACi) have been approved to treat some of them. In this study we investigated IgH locus transcription in B-cell splenocytes stimulated with LPS and the HDACi SAHA. B-cell development is spatially and temporally regulated with the 3'RR enhancer of the IgH locus as a conductor. 3'RR is composed of 4 enhancer elements with a palindromic structure of great significance. We investigated the role of this palindrome with KOKI mice where the 30Kb structure of the 3'RR has been deleted of its palindromic structure.

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