Title

Histone reader BRWD1 targets and restricts recombination to the Igk locus.

Document Type

Article

Publication Date

10-1-2015

JAX Source

Nat Immunol 2015 Oct; 16(10):1094-103.

Volume

16

Issue

10

First Page

1094

Last Page

1103

ISSN

1529-2916

PMID

26301565

Abstract

B lymphopoiesis requires that immunoglobulin genes be accessible to RAG1-RAG2 recombinase. However, the RAG proteins bind widely to open chromatin, which suggests that additional mechanisms must restrict RAG-mediated DNA cleavage. Here we show that developmental downregulation of interleukin 7 (IL-7)-receptor signaling in small pre-B cells induced expression of the bromodomain-family member BRWD1, which was recruited to a specific epigenetic landscape at Igk dictated by pre-B cell receptor (pre-BCR)-dependent Erk activation. BRWD1 enhanced RAG recruitment, increased gene accessibility and positioned nucleosomes 5' to each Jκ recombination signal sequence. BRWD1 thus targets recombination to Igk and places recombination within the context of signaling cascades that control B cell development. Our findings represent a paradigm in which, at any particular antigen-receptor locus, specialized mechanisms enforce lineage- and stage-specific recombination. Nat Immunol 2015 Oct; 16(10):1094-103.

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