| RRC ID |
37707
|
| Author |
Takemori Y, Enoki Y, Yamamoto N, Fukai Y, Adachi K, Sakurai H.
|
| Title |
Mutational analysis of human heat-shock transcription factor 1 reveals a regulatory role for oligomerization in DNA-binding specificity.
|
| Journal |
Biochem J
|
| Abstract |
HSF (heat-shock transcription factor) trimers bind to the HSE (heat-shock element) regulatory sequence of target genes and regulate gene expression. A typical HSE consists of at least three contiguous inverted repeats of the 5-bp sequence nGAAn. Yeast HSF is able to recognize discontinuous HSEs that contain gaps in the array of the nGAAn sequence; however, hHSF1 (human HSF1) fails to recognize such sites in vitro, in yeast and in HeLa cells. In the present study, we isolated suppressors of the temperature-sensitive growth defect of hHSF1-expressing yeast cells. Intragenic suppressors contained amino acid substitutions in the DNA-binding domain of hHSF1 that enabled hHSF1 to regulate the transcription of genes containing discontinuous HSEs. The substitutions facilitated hHSF1 oligomerization, suggesting that the DNA-binding domain is important for this conformational change. Furthermore, other oligomerization-prone derivatives of hHSF1 were capable of recognizing discontinuous HSEs. These results suggest that modulation of oligomerization is important for the HSE specificity of hHSF1 and imply that hHSF1 possesses the ability to bind to and regulate gene expression via various types of HSEs in diverse cellular processes.
|
| Volume |
424(2)
|
| Pages |
253-61
|
| Published |
2009-11-11
|
| DOI |
10.1042/BJ20090922
|
| PII |
BJ20090922
|
| PMID |
19758120
|
| MeSH |
Amino Acid Sequence
DNA / metabolism*
DNA-Binding Proteins / analysis
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
HeLa Cells
Heat Shock Transcription Factors
Humans
Molecular Sequence Data
Mutation*
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / growth & development
Saccharomyces cerevisiae / metabolism
Substrate Specificity
Transcription Factors / analysis
Transcription Factors / chemistry
Transcription Factors / genetics*
Transcription Factors / metabolism
|
| IF |
4.097
|
| Times Cited |
13
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
|
