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Multiway chromatin conformation analyses at the human immunoglobulin heavy chain locus reveal regulatory principles underlying somatic hypermutation [ATAC-Seq]

ABSTRACT: Multiway chromatin conformation analyses at the human immunoglobulin heavy chain locus reveal regulatory principles underlying somatic hypermutation [ATAC-Seq]

PROVIDER: PRJNA1132192 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29715834_1.fastq.gz	Fastqsanger.gz
	SRR29715834_2.fastq.gz	Fastqsanger.gz
	SRR29715835_1.fastq.gz	Fastqsanger.gz
	SRR29715835_2.fastq.gz	Fastqsanger.gz

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Project description:The generation of protective antibodies by somatic hypermutation (SHM) is essential for antibody maturation and adaptive immunity. SHM involves co-transcriptional mutagenesis of immunoglobulin variable (V) regions regulated by enhancers located hundreds of kilobases away. How 3D chromatin structure affects SHM is poorly understood. Here, we measure higher-order interactions on single alleles of the human immunoglobulin heavy chain locus (IGH) using Tri-C. We find that SHM is underpinned by a multiway hub wherein the V region is proximal to all enhancers. Cohesin-mediated loop extrusion is dispensable for IGH transcription and hub architecture. Transcription and mutagenesis of IGH switch regions, which are necessary for antibody class-switch recombination, creates new chromatin loops that can form without cohesin. However, these additional loops do not compromise hub integrity, V region transcription or SHM. Thus, antibody maturation occurs within a multiway hub accommodating several gene-enhancer loops wherein transcription and mutagenesis of different segments can occur non-competitively.

2025-06-16 | GSE271541 | GEO