Computational and Functional Analysis of Growth Hormone (GH)-Regulated Genes Identifies the Transcriptional Repressor B-Cell Lymphoma 6 (Bc16) as a Participant in GH-Regulated Transcription

For insight into transcriptional mechanisms mediating physiological responses to GH, data mining was performed on a profile of GH-regulated genes induced or inhibited at different times in highly responsive 3T3-F442A adipocytes. Gene set enrichment analysis indicated that GH-regulated genes are enriched in pathways including phosphoinositide and insulin signaling and suggested that suppressor of cytokine signaling 2 (SOCS2) and phosphoinositide 3′ kinase regulatory subunit p85α (Pik3r1) are important targets. Model-based Chinese restaurant clustering identified a group of genes highly regulated by GH at times consistent with its key physiological actions. This cluster included IGF-I, phosphoinositide 3′ kinase p85α, SOCS2, and cytokine-inducible SH2-containing protein. It also contains the most strongly repressed gene in the profile, B cell lymphoma 6 (Bcl6), a transcriptional repressor. Quantitative real-time PCR verified the strong decrease in Bcl6 mRNA after GH treatment and induction of the other gene...