DNA-binding factor CTCF and long-range gene interactions in V(D)J recombination and oncogene activation

Claudia Ribeiro De Almeida, Ralph Stadhouders, Supat Thongjuea, Eric Soler, Rudi W. Hendriks*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

28 Citations (Scopus)

Abstract

Regulation of V(D)J recombination events at immunoglobulin (Ig) and T-cell receptor loci in lymphoid cells is complex and achieved via changes in substrate accessibility. Various studies over the last year have identified the DNA-binding zinc-finger protein CCCTC-binding factor (CTCF) as a crucial regulator of long-range chromatin interactions. CTCF often controls specific interactions by preventing inappropriate communication between neighboring regulatory elements or independent chromatin domains. Although recent gene targeting experiments demonstrated that the presence of the CTCF protein is not required for the process of V(D)J recombination per se, CTCF turned out to be essential to control order, lineage specificity and to balance the Ig V gene repertoire. Moreover, CTCF was shown to restrict activity of κ enhancer elements to the Ig κ locus. In this review, we discuss CTCF function in the regulation of V(D)J recombination on the basis of established knowledge on CTCF-mediated chromatin loop domains in various other loci, including the imprinted H19-Igf2 locus as well as the complex β-globin, MHC class II and IFN-γ loci. Moreover, we discuss that loss of CTCF-mediated restriction of enhancer activity may well contribute to oncogenic activation, when in chromosomal translocations Ig enhancer elements and oncogenes appear in a novel genomic context.

Original languageEnglish
Pages (from-to)6209-6218
Number of pages10
JournalBlood
Volume119
Issue number26
Early online date26 Apr 2012
DOIs
Publication statusPublished - 28 Jun 2012

Bibliographical note

© 2012 by The American Society of Hematology

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