C/EBP activates the human corticotropin-releasing hormone gene promoter

Mol Cell Endocrinol. 1997 Oct 31;134(1):41-50. doi: 10.1016/s0303-7207(97)00170-6.

Abstract

The purpose of these studies was to identify whether transcription factors, associated with cytokine signalling, affected promoter activity of the corticotropin releasing hormone (CRH) gene. Fragments of a 3.6 kb sequence of the human CRH gene promoter were amplified by PCR and ligated upstream of a CAT reporter. These constructs were transfected into a variety of cell lines, either alone or together, with transcription factor expression vectors. Basal activity of a 3070 bp CRH promoter fragment was only seen in neuronal and lymphoblastoid cell lines. Promoter activity was increased by the transcription factors C/EBPbeta (NF-IL6) and more strongly, by C/EBPdelta (NF-IL6beta). Increased CRH promoter activity following phorbol ester treatment was inhibited by a dominant negative NF-IL6 mutant, showing that the effects of phorbol ester were principally mediated by C/EBP. Moreover, the inverse changes in the expression of CRH in the hypothalamus and spleens of arthritic rats were paralleled by similar inverse changes in NF-IL6beta expression in these organs. These data show that some transcription factors associated with cytokine signalling can also activate the CRH promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / metabolism
  • CCAAT-Enhancer-Binding Proteins
  • Cell Line
  • Corticotropin-Releasing Hormone / genetics*
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / pharmacology
  • DNA-Binding Proteins / physiology*
  • Humans
  • Hypothalamus / metabolism
  • Lymphocytes
  • Male
  • Monocytes
  • Mutation
  • Neurons
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Promoter Regions, Genetic / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins
  • STAT3 Transcription Factor
  • Spleen / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Trans-Activators / pharmacology
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcriptional Activation / physiology*
  • Transfection

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, rat
  • Trans-Activators
  • Transcription Factors
  • Corticotropin-Releasing Hormone
  • Tetradecanoylphorbol Acetate