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Heat shock factor‐4 (HSF‐4a) is a repressor of HSF‐1 mediated transcription *
Author(s) -
Zhang Yan,
Frejtag Wojciech,
Dai Rujuan,
Mivechi Nahid F.
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.1191
Subject(s) - heat shock factor , repressor , transcription factor , hspa12a , transcription (linguistics) , biology , promoter , microbiology and biotechnology , gene isoform , heat shock , heat shock protein , general transcription factor , gene expression , gene , hsp70 , genetics , linguistics , philosophy
Heat shock transcription factors (HSFs) regulate the expression of heat shock proteins and other molecular chaperones that are involved in cellular processes from higher order assembly to protein degradation and apoptosis. Among the human HSFs, HSF‐4 is expressed as at least two splice variants. One isoform (HSF‐4b) possesses a transcriptional activation domain, but this region is absent in the other isoform (HSF‐4a). We have recently shown that the HSF‐4a isoform represses basal transcription from heterologous promoters both in vitro and in vivo. Here we show that HSF‐4a and HSF‐4b have dramatically different effects on HSF‐1‐containing nuclear bodies, which form after heat shock. While the expression of HSF‐4b colocalizes with nuclear granules, the expression of HSF‐4a prevents their formation. In addition, there is a concurrent reduction of HSF‐1 in the nucleus, and there is reduction in its DNA binding activity and in HSE‐dependent transcription of a reporter gene. To better understand the mechanism by which HSF‐4a represses transcription, we inducibly expressed HSF‐4a in cells and found that HSF‐4a binds to the heat shock element (HSE) during attenuation of the heat shock response. Thus HSF‐4a is an active repressor of HSF‐1‐mediated transcription. This repressor function makes the HSF‐4a isoform unique within the HSF family. J. Cell. Biochem. 82: 692–703, 2001. © 2001 Wiley‐Liss, Inc.