The activation function 2 domain of hepatic nuclear factor 4 is regulated by a short C-terminal proline-rich repressor domain

Nucleic Acids Res. 1998 May 1;26(9):2098-104. doi: 10.1093/nar/26.9.2098.

Abstract

Hepatic nuclear factor 4 (HNF4) is a transcription factor whose expression is crucial for mouse embryonic development, for liver-specific gene expression and for the prevention of one form of maturity-onset diabetes of the young. Its domain structure has been defined previously and is similar to other members of the nuclear receptor superfamily. A repressor domain has now been localised to a region of 14 amino acids (residues 428-441) near the C-terminus of HNF4 and is sufficient by itself to repress the activity of the activation function 2 (AF2) domain. Multiple mutations within this repressor domain enhance activity. Interestingly, this repressor domain shares homology with a repressor domain in the progesterone receptor. In a detailed mutagenesis study of the AF2 core, we demonstrate that L 366, which is conserved in the AF2 core between HNF4 and a number of orphan nuclear receptors, is essential for the full activity of the AF2 domain. Furthermore, a double mutation of E 363 and L 366 suggests that these residues might act in a cooperative manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA Mutational Analysis
  • DNA-Binding Proteins*
  • Hepatocyte Nuclear Factor 4
  • Molecular Sequence Data
  • Mutagenesis
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Proline*
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • GAL4 protein, S cerevisiae
  • Hepatocyte Nuclear Factor 4
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Tcfl4 protein, mouse
  • Transcription Factors
  • Proline