Transcriptomics,Genomics

Dataset Information

597

Histone Reader BRWD1 Targets and Restricts Recombination to the Igk Locus


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–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. ChIP-seq for 1 transcription factor and 2 histone modifications in flow purified mouse small pre-B cells. ATAC-seq and RNA-seq in WT and Brwd-Mut mouse flow purified small pre-B cells.

ORGANISM(S): Mus musculus  

SUBMITTER: Malay Mandal   Marcus Clark  Mark Maienschein-Cline  Jeffrey J Bunker  Keith M Hamel  Grace Teng  John J Eppig  David G Schatz  Jigyasa H Tuteja  Neil Bahroos  Azusa Tanaka 

PROVIDER: E-GEOD-63302 | ArrayExpress | 2015-08-24

SECONDARY ACCESSION(S): GSE63302SRP049817PRJNA267245

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications


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-  ...[more]

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