Histone Reader BRWD1 Targets and Restricts Recombination to the Igk Locus

Overview

Journal Nat Immunol

Date 2015 Aug 25

PMID 26301565

Citations 26

Authors

Malay Mandal

Keith M Hamel

Mark Maienschein-Cline

Azusa Tanaka

Grace Teng

Jigyasa H Tuteja

Jeffrey J Bunker

Neil Bahroos

John J Eppig

David G Schatz

Marcus R Clark

Affiliations

Soon will be listed here.

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.

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References

Lewis S, Agard E, Suh S, Czyzyk L . Cryptic signals and the fidelity of V(D)J joining. Mol Cell Biol. 1997; 17(6):3125-36. PMC: 232165. DOI: 10.1128/MCB.17.6.3125. View

Spanopoulou E, Zaitseva F, Wang F, Santagata S, Baltimore D, Panayotou G . The homeodomain region of Rag-1 reveals the parallel mechanisms of bacterial and V(D)J recombination. Cell. 1996; 87(2):263-76. DOI: 10.1016/s0092-8674(00)81344-6. View

Kwon J, Imbalzano A, Matthews A, Oettinger M . Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1. Mol Cell. 1999; 2(6):829-39. DOI: 10.1016/s1097-2765(00)80297-x. View

Golding A, Chandler S, Ballestar E, Wolffe A, Schlissel M . Nucleosome structure completely inhibits in vitro cleavage by the V(D)J recombinase. EMBO J. 1999; 18(13):3712-23. PMC: 1171448. DOI: 10.1093/emboj/18.13.3712. View

Dunn K, Davie J . Stimulation of the Ras-MAPK pathway leads to independent phosphorylation of histone H3 on serine 10 and 28. Oncogene. 2005; 24(21):3492-502. DOI: 10.1038/sj.onc.1208521. View

Shogren-Knaak M, Ishii H, Sun J, Pazin M, Davie J, Peterson C . Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science. 2006; 311(5762):844-7. DOI: 10.1126/science.1124000. View

Cooper A, Sawai C, Sicinska E, Powers S, Sicinski P, Clark M . A unique function for cyclin D3 in early B cell development. Nat Immunol. 2006; 7(5):489-97. DOI: 10.1038/ni1324. View

Rahman N, Godderz L, Stray S, Capra J, Rodgers K . DNA cleavage of a cryptic recombination signal sequence by RAG1 and RAG2. Implications for partial V(H) gene replacement. J Biol Chem. 2006; 281(18):12370-80. DOI: 10.1074/jbc.M507906200. View

Cobb R, Oestreich K, Osipovich O, Oltz E . Accessibility control of V(D)J recombination. Adv Immunol. 2006; 91:45-109. DOI: 10.1016/S0065-2776(06)91002-5. View

10.

Abarrategui I, Krangel M . Regulation of T cell receptor-alpha gene recombination by transcription. Nat Immunol. 2006; 7(10):1109-15. DOI: 10.1038/ni1379. View

11.

Krangel M . T cell development: better living through chromatin. Nat Immunol. 2007; 8(7):687-94. DOI: 10.1038/ni1484. View

12.

Osipovich O, Cobb R, Oestreich K, Pierce S, Ferrier P, Oltz E . Essential function for SWI-SNF chromatin-remodeling complexes in the promoter-directed assembly of Tcrb genes. Nat Immunol. 2007; 8(8):809-16. DOI: 10.1038/ni1481. View

13.

Abarrategui I, Krangel M . Noncoding transcription controls downstream promoters to regulate T-cell receptor alpha recombination. EMBO J. 2007; 26(20):4380-90. PMC: 2034674. DOI: 10.1038/sj.emboj.7601866. View

14.

Liu Y, Subrahmanyam R, Chakraborty T, Sen R, Desiderio S . A plant homeodomain in RAG-2 that binds Hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement. Immunity. 2007; 27(4):561-71. PMC: 3711682. DOI: 10.1016/j.immuni.2007.09.005. View

15.

Matthews A, Kuo A, Ramon-Maiques S, Han S, Champagne K, Ivanov D . RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature. 2007; 450(7172):1106-10. PMC: 2988437. DOI: 10.1038/nature06431. View

16.

Zhang M, Swanson P . V(D)J recombinase binding and cleavage of cryptic recombination signal sequences identified from lymphoid malignancies. J Biol Chem. 2008; 283(11):6717-27. DOI: 10.1074/jbc.M710301200. View

17.

Johnson K, Hashimshony T, Sawai C, Pongubala J, Skok J, Aifantis I . Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling. Immunity. 2008; 28(3):335-45. DOI: 10.1016/j.immuni.2007.12.019. View

18.

Philipps D, Wigglesworth K, Hartford S, Sun F, Pattabiraman S, Schimenti K . The dual bromodomain and WD repeat-containing mouse protein BRWD1 is required for normal spermiogenesis and the oocyte-embryo transition. Dev Biol. 2008; 317(1):72-82. PMC: 2475337. DOI: 10.1016/j.ydbio.2008.02.018. View

19.

Du H, Ishii H, Pazin M, Sen R . Activation of 12/23-RSS-dependent RAG cleavage by hSWI/SNF complex in the absence of transcription. Mol Cell. 2008; 31(5):641-9. PMC: 4589277. DOI: 10.1016/j.molcel.2008.08.012. View

20.

Jiang C, Pugh B . Nucleosome positioning and gene regulation: advances through genomics. Nat Rev Genet. 2009; 10(3):161-72. PMC: 4860946. DOI: 10.1038/nrg2522. View