Cell-type specific activity of two glucocorticoid responsive units of rat tyrosine aminotransferase gene is associated with multiple binding sites for C/EBP and a novel liver-specific nuclear factor

Nucleic Acids Res. 1991 Jan 11;19(1):131-9. doi: 10.1093/nar/19.1.131.

Abstract

The structures of two remote glucocorticoid responsive units (GRUs) that cooperatively interact to promote cell-type specific glucocorticoid induction of rat tyrosine aminotransferase gene expression have been analyzed. DNAase I footprinting and gel mobility shift analyses reveal a complex array of contiguous and overlapping sites for cell type-specific DNA binding proteins. Apart from the glucocorticoid receptor, two liver-specific nuclear factors possess multiple binding sites in each of these GRUs: C/EBP and a newly identified liver-specific factor: HNF5. C/EBP possesses four binding sites in each GRU; a DNA-binding protein with similar binding specificity has been identified in fibroblasts; this protein could be related to AP-3. HNF5 possesses two binding sites in one GRU and four in the other. There are also HNF5 binding sites in numerous regulatory regions of other liver-specific genes. The interaction of HNF5 with DNA gives a characteristic DNAase I footprint with hypersensitive sites in the middle of the recognition sequence. Some of the C/EBP and HNF5 binding sites overlap in a conserved arrangement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Binding, Competitive
  • CCAAT-Enhancer-Binding Proteins
  • DNA
  • DNA-Binding Proteins / metabolism*
  • Deoxyribonuclease I / metabolism
  • Glucocorticoids / metabolism*
  • Liver / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Organ Specificity
  • Rats
  • Transcription Factors / metabolism*
  • Tyrosine Transaminase / genetics*
  • Tyrosine Transaminase / metabolism

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Glucocorticoids
  • Nuclear Proteins
  • Transcription Factors
  • DNA
  • Tyrosine Transaminase
  • Deoxyribonuclease I