In:
The Journal of Immunology, The American Association of Immunologists, Vol. 179, No. 8 ( 2007-10-15), p. 5264-5273
Abstract:
The 3-megabase Igκ locus undergoes differentially controlled nuclear positioning events and chromatin structural changes during the course of B cell development. The temporal association of chromatin structural changes, transcription, and recombination at the Igκ locus was determined in a murine pre-B cell line that can be induced to recombine at the Igκ locus and in ex vivo-cultured murine pre-B cells. Additionally, the timing of nuclear positioning relative to the temporal order of chromatin structural changes and recombination and transcription was determined. We demonstrate that before induction, the Igκ locus was poised for recombination; both alleles were in a contracted state, and the enrichment of histone modifications and germline transcripts of specific Vκ genes were observed. Histone modifications of the Vκ genes did not vary upon induction but the levels of modifications correlated with the levels of germline Vκ gene transcripts and recombination. Upon induction, but before VκJκ recombination, centromeric recruitment of single Igκ alleles occurred. DNase I sensitivity of the entire locus increased gradually over the course of differentiation while the enrichment of histone modifications downstream of the Vκ genes was increased in the silencer regions upstream of Jκ1, within the Igκ sterile transcript, the κ constant region, the Eκi and Eκ3′ enhancers, and the recombining sequence. The ex vivo pre-B cells showed similar patterns of histone modifications across the locus except at the Vκ genes. In this study, H3 acetylation correlated with levels of germline transcripts while H3 methylation correlated with levels of recombination.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.179.8.5264
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2007
detail.hit.zdb_id:
1475085-5
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