C/EBPβ mediates growth hormone-regulated expression of multiple target genes

Mol Endocrinol. 2011 Apr;25(4):681-93. doi: 10.1210/me.2010-0232. Epub 2011 Feb 3.


Regulation of c-Fos transcription by GH is mediated by CCAAT/enhancer binding protein β (C/EBPβ). This study examines the role of C/EBPβ in mediating GH activation of other early response genes, including Cyr61, Btg2, Socs3, Zfp36, and Socs1. C/EBPβ depletion using short hairpin RNA impaired responsiveness of these genes to GH, as seen for c-Fos. Rescue with wild-type C/EBPβ led to GH-dependent recruitment of the coactivator p300 to the c-Fos promoter. In contrast, rescue with C/EBPβ mutated at the ERK phosphorylation site at T188 failed to induce GH-dependent recruitment of p300, indicating that ERK-mediated phosphorylation of C/EBPβ at T188 is required for GH-induced recruitment of p300 to c-Fos. GH also induced the occupancy of phosphorylated C/EBPβ and p300 on Cyr61, Btg2, and Socs3 at predicted C/EBP-cAMP response element-binding protein 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/EBPβ. A subset of these genes is regulated similarly to c-Fos, through a mechanism involving GH-stimulated ERK 1/2 activation, phosphorylation of C/EBPβ, and recruitment of p300. Overall, these studies suggest that C/EBPβ, like the signal transducer and activator of transcription proteins, regulates multiple genes in response to GH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Butadienes / pharmacology
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cell Line
  • Chromatin Immunoprecipitation
  • Cricetinae
  • Cricetulus
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation*
  • Genes, fos / genetics
  • Growth Hormone / metabolism*
  • Immunoblotting
  • Mice
  • Mutation
  • Nitriles / pharmacology
  • Phosphorylation
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • RNA, Small Interfering
  • Response Elements
  • Signal Transduction / genetics
  • Transcriptional Activation
  • p300-CBP Transcription Factors / metabolism


  • Butadienes
  • CCAAT-Enhancer-Binding Protein-beta
  • Cebpb protein, mouse
  • Nitriles
  • RNA, Small Interfering
  • U 0126
  • Growth Hormone
  • p300-CBP Transcription Factors
  • Extracellular Signal-Regulated MAP Kinases