Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2195998 | Molecular and Cellular Endocrinology | 2014 | 13 Pages |
•BCL6 and STAT5 reciprocally occupy Socs2, Cish and Bcl6 promoters in response to GH.•Socs2 and Cish expression increase with GH while Bcl6 expression is inhibited.•BCL6 potently inhibits Socs2, Cish and Bcl6 promoters.•p300 co-activates and HDAC3 inhibits STAT5 induction of Socs2 and Cish.•Both p300 and HDAC3 repress STAT5 on the Bcl6 promoter.
Expression of the Growth Hormone (GH)-stimulated gene Socs2 (Suppressor of Cytokine Signaling 2) is mediated by the transcription activator STAT5 (Signal Transducer and Activator of Transcription 5) and the transcription repressor BCL6 (B-Cell Lymphoma 6). ChIP-Sequencing identified Cish (Cytokine-Inducible SH2-containing protein) and Bcl6 as having similar patterns of reciprocal occupancy by BCL6 and STAT5 in response to GH, though GH stimulates Cish and inhibits Bcl6 expression. The co-activator p300 occupied Socs2, Cish and Bcl6 promoters, and enhanced STAT5-mediated activation of Socs2 and Cish. In contrast, on Bcl6, p300 functioned as a repressor and inhibited in conjunction with STAT5 or BCL6. The co-repressor HDAC3 (Histone deacetylase 3) inhibited the Socs2, Cish and Bcl6 promoters in the presence of STAT5. Thus transcriptional outcomes on GH-regulated genes occupied by BCL6 and STAT5 are determined in a promoter-specific fashion by co-regulatory proteins which mediate the distinction between activating and repressive transcription factors.