title: Set1/MLL complex is indispensable for the transcriptional ability of heat shock transcription factor 2.
abstract: Heat shock transcription factor 2 (HSF2) is one of four mammalian HSFs, and it is essential in neurogenesis and gametogenesis. However, other aspects of this transcription factor have not been thoroughly characterized. We recently demonstrated that HSF2 suppresses the aggregation caused by polyglutamine (polyQ) protein, and that the cell protective ability of HSF2 is mediated through the induction of the small HSP alphaB-crystallin (CRYAB). In the present study, we investigated the mechanism of HSF2-induced CRYAB expression. We demonstrated that HSF2 interacted with the core component of the Set1/MLL H3K4 histone methyltransferase complex, WDR5. Indeed, HSF2 up-regulated the H3K4me3, H3K14Ac, and H3K27Ac (active histone marks) of the CRYAB promoter. WDR5 bound to the HSF2 central domain (Domain X) in vitro and in vivo, and Cys278 of HSF2 was indispensable for HSF2-WDR5 interaction. HSF2 also interacted with the Set1/MLL complex. These results suggest that the interaction with the Set1/MLL complex via binding to WDR5 is critical for the transcriptional ability of HSF2.
authors.affiliation: Department of Biochemistry, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. Electronic address: hayasida@yamaguchi-u.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashida
mesh_terms: D001483:Base Sequence; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism
chemical_list: C059215:CRYAB protein, human; D002843:Chromatin; C525420:Cryab protein, mouse; D004268:DNA-Binding Proteins; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D006657:Histones; C531390:Hsf2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C497422:KMT2A protein, human; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D014157:Transcription Factors; C502547:WDR5 protein, human; D038203:alpha-Crystallin B Chain; C070389:HSF2 protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse; C526068:Setd1A protein, human; D008239:Lysine
keywords: Acetylation; HSF2; Histone; Set1/MLL complex; Trimethylation; WDR5