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Publication : Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments.

First Author  Hesslein DG Year  2003
Journal  Genes Dev Volume  17
Issue  1 Pages  37-42
PubMed ID  12514097 Mgi Jnum  J:81181
Mgi Id  MGI:2448212 Doi  10.1101/gad.1031403
Citation  Hesslein DG, et al. (2003) Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments. Genes Dev 17(1):37-42
abstractText  Pax5-deficient progenitor B (pro-B) cells are thought to be severely defective for recombination of all immunoglobulin heavy chain (IgH) V gene segments, but the mechanism by which Pax5 regulates this process has not been defined. To address this issue, we have examined the assembly of the IgH locus in Pax5-deficient pro-B cells and find, unexpectedly, that 3' IgH V gene segments, which lie closest to the D-J-Cmu region, recombine efficiently, but progressively more distal V gene segments recombine progressively less efficiently. Histone acetylation and germ-line transcription correlate strongly with an open or an accessible chromatin structure thought to be permissive for V(D)J recombination, and defects in recombination are typically accompanied by deficits in these processes. We were therefore surprised to observe that distal V(H) gene segments in Pax5-/- pro-B cells exhibit no defect in these measures of accessibility. The finding of transcribed, histone acetylated gene segments that fail to recombine suggests that a Pax5-dependent regulatory mechanism is required in addition to standard constraints of accessibility to control V(H) gene recombination.
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