Nucleic Acids Research, Vol 26, Issue 9 2098-2104, Copyright © 1998 by Oxford University Press
VP Iyemere, NH Davies and GG Brownlee
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.
ARTICLES
The activation function 2 domain of hepatic nuclear factor 4 is regulated by a short C-terminal proline-rich repressor domain
Chemical Pathology Unit, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
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