C/EBP beta mediates growth hormone-regulated expression of multiple target genes.

TRACY X. CUI; GRACE LIN; CHRISTOPHER R. LAPENSEE; ANDA-ALEXANDRA CALINESCU; MAANJOT RATHORE; CALE STREETER; GRACIELA PIWIEN PILIPUK; NATHAN LANNING; HUI JIN; CHRISTIN CARTER-SU; ZHAOHUI S. QIN; JESSICA SCHWARTZ

MOLECULAR ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2011 vol. 25 p. 681 - 693

0888-8809

Regulation of c-Fos transcription by GH is mediated by C/EBPb.  This study examines the role of C/EBPb in mediating GH activation of other early response genes including Cyr61, Btg2, Socs3, Zfp36 and Socs1.  C/EBPb depletion using shRNA impaired responsiveness of these genes to GH, as seen for c-Fos.  Rescue with wild-type C/EBPbeta led to GH-dependent recruitment of the co-activator p300 to the c-Fos promoter.  In contrast, rescue with C/EBPbeta mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBP beta at T188 is required for GH-induced recruitment of p300 to c-Fos.  GH also induced the occupancy of phosphorylated C/EBPb and p300 on Cyr61, Btg2 and Socs3 at predicted C/EBP-CREB motifs in their promoters. Consistent with a role for ERKs in GH-induced expression of these genes, treatment with U0126 to block ERK phosphorylation inhibited their GH-induced expression.  In contrast, GH-dependent expression of Zfp36 and Socs1 was not inhibited by U0126.  Thus induction of multiple early response genes by GH in 3T3-F442A cells is mediated by C/EBPb.  A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPbeta and recruitment of p300.  Overall, these studies suggest that C/EBPbeta, like the Stat proteins, regulates multiple genes in response to GH