Nucleic Acids Research, Vol 25, Issue 22 4455-4463, Copyright © 1997 by Oxford University Press
PA Defossez, JL Baert, M Monnot and Y de Launoit
Transcription factors are modular entities built up of discrete domains,
some devoted to DNA binding and others permitting transcriptional
modulation. The structure of DNA binding domains has been thoroughly
investigated and structural classes clearly defined. In sharp contrast, the
structural constraints put on transactivating regions, if any, are mostly
unknown. Our investigations focus on ERM, a eukaryotic transcription factor
of the ETS family. We have previously shown that ERM harbours two
transactivating domains (TADs) with distinct functional features: AD1 lies
in the first 72 amino acids of ERM, while AD2 sits in the last 62. Here we
show that AD1 is a bona fide acidic TAD, for it activated transcription in
yeast cells, while AD2 did not. AD1 contains a 20 amino acid stretch
predicted to form an alpha-helix that is found unchanged in the related
PEA3 and ER81 transcription factors. Circular dichroism analysis revealed
that a 32 amino acid peptide encompassing this region is unstructured in
water but folds into a helix when the hydrophobic solvent trifluoroethanol
is added. The isolated helix was sufficient to activate transcription and
mutations predicted to disrupt it dramatically affected AD1-driven
transactivation, whereas mutations decreasing its acidity had more gentle
effects. A phenylalanine residue within the helix was particularly
sensitive to mutations. Finally, we observed that ERM bound TAFII60 via AD1
and bound TBP and TAFII40, presumably via other activation domains.
ARTICLES
The ETS family member ERM contains an alpha-helical acidic activation domain that contacts TAFII60
Mecanismes du Developpement et de la Cancerisation, UMR 319 CNRS/Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue Calmette, BP 447, 59021 Lille Cedex, France.
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