Stat5 mediates the IL-7-induced accessibility of a representative D-Distal VH gene.
During B cell development, discrete domains within the Igh locus are activated independently for recombination. The D-distal V(H) genes are uniquely dependent on IL-7R signaling, which is thought to establish local chromatin accessibility through an unknown mechanism. To dissect this mechanism, we used a murine B cell line that responds to IL-7 by specifically inducing accessibility of a representative D-distal gene (A1) but not a D-proximal gene (V11). We demonstrate that IL-7-activated Stat5 is recruited rapidly to the A1 gene, with a concomitant increase in germline transcription and H4 acetylation. Furthermore, retroviral transduction of dominant negative or constitutively active Stat5 demonstrated that Stat5 activation is both necessary and sufficient for the IL-7-induced A1 germline transcription. Lastly, as with all known Stat5 target genes, A1 germline transcription requires a deacetylase activity. These results demonstrate that in response to IL-7 signaling, Stat5 is recruited to the D-distal A1 gene and induces accessibility.
Stanton
Michelle L
ML
Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
Brodeur
Peter H
PH
D000107:Acetylation; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002472:Cell Transformation, Viral; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005803:Genes, Immunoglobulin; D006657:Histones / Q000378:metabolism; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D008894:Milk Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology
D016207:Cytokines; D004268:DNA-Binding Proteins; D006657:Histones; D015851:Interleukin-7; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide