RPA assists HSF1 access to nucleosomal DNA by recruiting histone chaperone FACT

Mitsuaki Fujimoto; Eiichi Takaki; Ryosuke Takii; Ke Tan; Ramachandran Prakasam; Naoki Hayashida; Shun-ichiro Iemura; Tohru Natsume; Akira Nakai

doi:10.1016/j.molcel.2012.07.026

RPA assists HSF1 access to nucleosomal DNA by recruiting histone chaperone FACT

Mol Cell. 2012 Oct 26;48(2):182-94. doi: 10.1016/j.molcel.2012.07.026. Epub 2012 Aug 30.

Authors

Mitsuaki Fujimoto¹, Eiichi Takaki, Ryosuke Takii, Ke Tan, Ramachandran Prakasam, Naoki Hayashida, Shun-ichiro Iemura, Tohru Natsume, Akira Nakai

Affiliation

¹ Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube 755-8505, Japan.

PMID: 22940245
DOI: 10.1016/j.molcel.2012.07.026

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Base Sequence
Chromatin / genetics
DNA / genetics
DNA / metabolism
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Gene Expression Regulation*
HEK293 Cells
Heat Shock Transcription Factors
High Mobility Group Proteins* / genetics
High Mobility Group Proteins* / metabolism
Humans
Molecular Sequence Data
Nucleosomes / genetics
Promoter Regions, Genetic
Protein Binding
Protein Interaction Domains and Motifs / genetics
RNA Polymerase II / metabolism
Regulatory Elements, Transcriptional*
Replication Protein A / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcriptional Elongation Factors* / genetics
Transcriptional Elongation Factors* / metabolism

Substances

Chromatin
DNA-Binding Proteins
HSF1 protein, human
Heat Shock Transcription Factors
High Mobility Group Proteins
Nucleosomes
Replication Protein A
SSRP1 protein, human
Transcription Factors
Transcriptional Elongation Factors
DNA
RNA Polymerase II

Associated data

GEO/GSE38412