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. 1998 May 1;26(9):2098–2104. doi: 10.1093/nar/26.9.2098

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

V P Iyemere 1, N H Davies 1, G G Brownlee 1
PMCID: PMC147528  PMID: 9547266

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.

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Selected References

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