The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Pax5 induces V -to- DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene
Open accessAbstract
The subnuclear location and chromatin state of the immunoglobulin heavy-chain ( IgH ) locus have been implicated in the control of V(D)J recombination. V H -to- DJ H rearrangement of distal, but not proximal V H genes, furthermore, depends on the B-lineage commitment factor Pax5 (BSAP). Here we demonstrate that ectopic Pax5 expression from the Ikaros promoter induces proximal rather than distal V H –DJ H rearrangements in Ik Pax5 /+ thymocytes, thus recapitulating the loss-of-function phenotype of Pax5 –/– pro-B cells. The phenotypic similarities of both cell types include (1) chromatin accessibility of distal V H genes in the absence of V H –DJ H rearrangements, (2) expression of the B-cell-specific regulator EBF, (3) central location of IgH alleles within the nucleus, and (4) physical separation of distal V H genes from proximal segments in an extended IgH locus. Reconstitution of Pax5 expression in Pax5 –/– pro-B cells induced large-scale contraction and distal V H –DJ H rearrangements of the IgH locus. Hence, V H –DJ H recombination is regulated in two steps during early B-lymphopoiesis. The IgH locus is first repositioned from its default location at the nuclear periphery toward the center of the nucleus, which facilitates proximal V H –DJ H recombination. Pax5 subsequently activates locus contraction and distal V H –DJ H rearrangements in collaboration with an unknown factor that is present in pro-B cells, but absent in thymocytes.
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Yin Yang 1 is a critical regulator of B-cell development
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Metadata
- Authors
- Fuxa, M., Skok, J., Souabni, A., Salvagiotto, G., Roldan, E., & Busslinger, M.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-02-15
- Volume
- 18
- Issue
- 4
- Pages
- 411-422
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W1995955910
- Cited by
- 414
- References
- 54
- Type
- posted content
- Language
- en
- Open access
- diamond
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