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IGH analysis in pro-B cells with H3K4me3, H3K4me2 and H3K9ac

ABSTRACT: STAT5 and IL-7 signaling are thought to control B-lymphopoiesis by regulating key transcription factor genes and activating VH gene segments at the Igh locus. Using conditional mutagenesis, we demonstrate that transgenic Bcl2 expression rescued the development of Stat5-deleted pro-B cells by compensating for the loss of Mcl-1. Ebf1 and Pax5 expression as well as VH recombination were normal in Bcl2-rescued pro-B cells lacking STAT5 or IL-7Ra. In agreement with this finding, STAT5-expressing pro-B cells contained little or no active chromatin at most VH genes. In contrast, Igk rearrangements were increased in STAT5- or IL-7Ra-deficient pro-B cells, consistent with direct binding of STAT5 to the intronic iEk enhancer in wild-type pro-B cells. Hence, STAT5 and IL-7 signaling control cell survival and suppress premature Igk recombination in early B-lymphopoiesis. comparison of wt vs Rag2-/- pro-B cells

ORGANISM(S): Mus musculus

SUBMITTER: Meinrad Busslinger 

PROVIDER: E-GEOD-18278 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development.

Malin Stephen S   McManus Shane S   Cobaleda César C   Novatchkova Maria M   Delogu Alessio A   Bouillet Philippe P   Strasser Andreas A   Busslinger Meinrad M  

Nature immunology 20091129 2

STAT5 and interleukin 7 (IL-7) signaling are thought to control B lymphopoiesis by regulating the expression of key transcription factors and by activating variable (V(H)) gene segments at the immunoglobulin heavy-chain (Igh) locus. Using conditional mutagenesis to delete the gene encoding the transcription factor STAT5, we demonstrate that the development of pro-B cells was restored by transgenic expression of the prosurvival protein Bcl-2, which compensated for loss of the antiapoptotic protei  ...[more]

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