CTCF-binding Elements Mediate Control of V(D)J Recombination

Overview

Journal Nature

Specialty Science

Date 2011 Sep 13

PMID 21909113

Citations 172

Authors

Chunguang Guo

Hye Suk Yoon

Andrew Franklin

Suvi Jain

Anja Ebert

Hwei-Ling Cheng

Erica Hansen

Orion Despo

Claudia Bossen

Christian Vettermann

Jamie G Bates

Nicholas Richards

Darienne Myers

Harin Patel

Michael Gallagher

Mark S Schlissel

Cornelis Murre

Meinrad Busslinger

Cosmas C Giallourakis

Frederick W Alt

Affiliations

Soon will be listed here.

Abstract

Immunoglobulin heavy chain (IgH) variable region exons are assembled from V(H), D and J(H) gene segments in developing B lymphocytes. Within the 2.7-megabase mouse Igh locus, V(D)J recombination is regulated to ensure specific and diverse antibody repertoires. Here we report in mice a key Igh V(D)J recombination regulatory region, termed intergenic control region 1 (IGCR1), which lies between the V(H) and D clusters. Functionally, IGCR1 uses CTCF looping/insulator factor-binding elements and, correspondingly, mediates Igh loops containing distant enhancers. IGCR1 promotes normal B-cell development and balances antibody repertoires by inhibiting transcription and rearrangement of D(H)-proximal V(H) gene segments and promoting rearrangement of distal V(H) segments. IGCR1 maintains ordered and lineage-specific V(H)(D)J(H) recombination by suppressing V(H) joining to D segments not joined to J(H) segments, and V(H) to DJ(H) joins in thymocytes, respectively. IGCR1 is also required for feedback regulation and allelic exclusion of proximal V(H)-to-DJ(H) recombination. Our studies elucidate a long-sought Igh V(D)J recombination control region and indicate a new role for the generally expressed CTCF protein.

Citing Articles

Interplay between CTCF-binding and CTCF-lacking regulatory elements in generating an architectural stripe at the Igh locus.

Ma F, Ollikainen N, Du H, Braikia F, Cui N, Bianchi A Nat Commun. 2025; 16(1):2148.

PMID: 40032827 PMC: 11876664. DOI: 10.1038/s41467-025-57373-w.

Dynamic O-GlcNAcylation governs long-range chromatin interactions in V(D)J recombination during early B-cell development.

Jeon B, Kim Y, Park A, Song M, Na K, Lee J Cell Mol Immunol. 2024; 22(1):68-82.

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Brain and cancer associated binding domain mutations provide insight into CTCF's relationship with chromatin and its ability to act as a chromatin organizer.

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Addressing Technical Pitfalls in Pursuit of Molecular Factors That Mediate Immunoglobulin Gene Regulation.

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