title: RPA assists HSF1 access to nucleosomal DNA by recruiting histone chaperone FACT.
abstract: Transcription factor access to regulatory elements is prevented by the nucleosome. Heat shock factor 1 (HSF1) is a winged helix transcription factor that plays roles in control and stressed conditions by gaining access to target elements, but mechanisms of HSF1 access are not well known in mammalian cells. Here, we show the physical interaction between the wing motif of human HSF1 and replication protein A (RPA), which is involved in DNA metabolism. Depletion of RPA1 abolishes HSF1 access to the promoter of HSP70 in unstressed condition and delays its rapid activation in response to heat shock. The HSF1-RPA complex leads to preloading of RNA polymerase II and opens the chromatin structure by recruiting a histone chaperone, FACT. Furthermore, this interaction is required for melanoma cell proliferation. These results provide a mechanism of constitutive HSF1 access to nucleosomal DNA, which is important for both basal and inducible gene expression.
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube 755-8505, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Eiichi
authors.initials: E
authors.lastname: Takaki
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takii
authors.forename: Ke
authors.initials: K
authors.lastname: Tan
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Prakasam
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashida
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D000076249:Heat Shock Transcription Factors; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D051716:Replication Protein A / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006609:High Mobility Group Proteins; D009707:Nucleosomes; D051716:Replication Protein A; C073537:SSRP1 protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D004247:DNA; D012319:RNA Polymerase II