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Reciprocal patterns of rnethylation H3K36 and H3K27 and on proximal vs. Distal IgVH modulated by IL-7 and Pax5

Academic Article
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Overview

authors

  • Xu, C. R.
  • Schaffer, L.
  • Head, Steve
  • Feeney, Ann

publication date

  • 2008

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • The usage of >100 functional murine Ig heavy chain V(H) genes, when rearranged to D(H)J(H) genes, generates a diverse antibody repertoire. The V(H) locus encompasses 2.5 Mb, and rearrangement of V(H) genes in the D(H)-distal half of the locus are controlled very differently from the V(H) genes in the proximal end of the locus. The rearrangement of distal but not proximal V(H) genes is impaired in mice deficient in the cytokine IL-7 or its receptor, in the transcription factor Pax5, or in Ezh2, a histone methyltransferase for Lys-27 of histone H3 (H3K27). The relative role of IL-7, Pax5, and Ezh2 in regulating distal vs. proximal V(H) rearrangement is not clear. Here, we show by ChIP and ChIP-on-chip that the active histone modification H3K36me2 is most highly associated with distal V(H) segments and the repressive histone modification H3K27me3 is exclusively present on proximal V(H) segments. We observed an absence of H3K27me3 in fetal pro-B cells, which predominantly rearrange proximal V(H) genes. Absence of IL-7 signaling reduces H3K36me2, and overexpression of IL-7 increases H3K36me2. In contrast, the major effect of the absence of Pax5 is the reduction in H3K27me3. Our data indicate that the cytokine IL-7 and the transcription factor Pax5 influence the rearrangement of the two regions of the V(H) locus by differentially modulating two reciprocal histone modifications during B lymphocyte development.

subject areas

  • Animals
  • B-Cell-Specific Activator Protein
  • B-Lymphocytes
  • Cell Line
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin Heavy Chain
  • Histone-Lysine N-Methyltransferase
  • Histones
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Interleukin-7
  • Methylation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Polycomb Repressive Complex 2
  • Proteins
  • Signal Transduction
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Identity

PubMed Central ID

  • PMC2438410

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0711758105

PubMed ID

  • 18562282
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Additional Document Info

start page

  • 8685

end page

  • 8690

volume

  • 105

issue

  • 25

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