Endogenous CCAAT/enhancer binding protein and p300 are both regulated by growth hormone to mediate transcriptional activation

Tracy Xiao Cui, Graciela Piwien-Pilipuk, Jeffrey S. Huo, Julianne Kaplani, Roland Kwok, Jessica Schwartz

Research output: Contribution to journalArticlepeer-review

Abstract

The regulation of c-fos transcription by GH involves multiple factors, including CCAAT/enhancer binding protein (C/EBP) β. Knockdown of C/EBPβ by RNA interference prevents stimulation of endogenous c-fos mRNA by GH, indicating a key role for C/EBPβ in GH-stimulated c-fos transcription. GH rapidly increases the occupancy of both endogenous C/EBPβ and p300 on the c-fos promoter in 3T3-F442A preadipocytes as indicated by chromatin immunoprecipitation. The transient occupancy of p300 on c-fos and the presence of p300 in the anti-C/EBPβ immunoprecipitate coincide with the transient increase in c-fos transcription with GH, suggesting that a nuclear complex containing both p300 and C/EBPβ occupies the c-fos promoter in response to GH. Expression of p300 with C/EBPβ markedly increases c-fos promoter activity when neither alone is effective, indicating that p300 coactivates C/EBPβ-mediated c-fos promoter activation. Such coactivation can determine a baseline for c-fos activation by GH. Furthermore, the occupancy of phosphorylated murine C/EBPβ (T188) on c-fos upon GH treatment is simultaneous with increased occupancy by p300, suggesting that phospho-C/EBPβ recruits p300 in response to GH. Thus, endogenous C/EBPβ and p300 on c-fos are dynamically regulated by GH to determine transcriptional activation. Phosphorylated C/EBPβ and p300 appear to function as part of a regulated complex that mediates GH-stimulated transcription.

Original languageEnglish (US)
Pages (from-to)2175-2186
Number of pages12
JournalMolecular Endocrinology
Volume19
Issue number8
DOIs
StatePublished - Aug 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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