Chromatin acetylation and remodeling at the Cis promoter during STAT5-induced transcription.
The signal transducer and activator of transcription STAT5 plays a major role in cytokine-induced expression of genes involved in cell proliferation and survival. Although several STAT5 partners have been identified, the molecular events taking place at the promoter level upon STAT5 recruitment have not yet been characterized in great detail. Using chromatin immunoprecipitation and accessibility assays, we characterized histone acetylation and chromatin remodeling events occurring during transcriptional activation of the endogenous murine Cis gene, a STAT5 target gene, in response to IL-3. We found that STAT5 binding in vivo is associated with low histone H3 and H4 acetylation levels in the proximity of the STAT5 binding sites. STAT5 recruitment also results in chromatin reorganization over that promoter region. These events (STAT5 binding, histone acetylation and chromatin remodeling) are not sufficient for transcriptional activation, which requires a non-histone protein deacetylase. These data reveal novel implications of STAT5 in chromatin regulation during cytokine-induced transcription, thus contributing to a better understanding of the mechanism of transcriptional activation by STAT5.
Rascle
Anne
A
Department of Discovery Research, DNAX Research Inc., 901 California Avenue, Palo Alto, CA 94304, USA.
Lees
Emma
E
D000107:Acetylation; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics*; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D008894:Milk Proteins; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D050799:STAT5 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
D002843:Chromatin; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D007377:Interleukin-3; D008894:Milk Proteins; D016760:Proto-Oncogene Proteins c-fos; D050799:STAT5 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; C494093:Stat5a protein, mouse