Tài liệu Báo cáo khoa học: Novel aspects of heat shock factors: DNA recognition, chromatin

MINIREVIEW

Novel aspects of heat shock factors: DNA recognition,

chromatin modulation and gene expression

Hiroshi Sakurai and Yasuaki Enoki

Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan

Background

The heat shock factor (HSF) in eukaryotes is involved

not only in heat shock protein (HSP) gene expression

and stress resistance, but also in the expression of

genes with roles in cell maintenance and differentia￾tion, as well as in developmental processes. HSF forms

a homotrimer that binds to gene promoters containing

a heat shock element (HSE), which is composed of

multiple inverted repeats of the pentanucleotide motif

nGAAn. Functional conservation of HSFs among

eukaryotes has been revealed by the finding that HSFs

from various organisms, including insects, mammals

and plants, can substitute for yeast HSF in Saccharo￾myces [1–4].

HSF proteins contain two evolutionarily conserved

functional modules: the DNA-binding domain (DBD)

at the amino-terminus and the oligomerization domain

in the central region of the protein [1,4]. The HSF

DBD belongs to the ‘winged’ helix-turn-helix family of

DNA-binding proteins and contains a three-helix bun￾dle capped by a four-stranded antiparallel b-sheet, and

a flexible loop or ‘wing’ with a less ordered structure

(Fig. 1) [5,6]. The second and third a-helices comprise

the helix-turn-helix motif. The oligomerization domain

consists of arrays of hydrophobic heptad repeats

(HRs), characteristic of helical coiled-coil structures

[1,4,7]. The HRs are divided into two subdomains:

HR-A and HR-B. The amino-terminal HR-A has

the potential to form trimers independently of HR-B,

and the carboxy-terminal HR-B can form large

oligomers [7].

Keywords

chromatin; heat shock element; heat shock

transcription factor; histone; protein–DNA

interactions

Correspondence

H. Sakurai, Department of Clinical

Laboratory Science, Kanazawa University

Graduate School of Medical Science,

5-11-80 Kodatsuno, Kanazawa, Ishikawa

920-0942, Japan

Fax: +81 76 234 4369

Tel: +81 76 265 2588

E-mail: [email protected]

(Received 10 May 2010, revised 9 July

2010, accepted 23 July 2010)

doi:10.1111/j.1742-4658.2010.07829.x

Heat shock factor (HSF) is an evolutionarily conserved stress-response reg￾ulator that activates the transcription of heat shock protein genes, whose

products maintain protein homeostasis under normal physiological condi￾tions, as well as under conditions of stress. The promoter regions of the

target genes contain a heat shock element consisting of multiple inverted

repeats of the pentanucleotide sequence nGAAn. A single HSF of yeast

can bind to heat shock elements that differ in the configuration of the

nGAAn units and can regulate the transcription of various genes that func￾tion not only in stress resistance, but also in a broad range of biological

processes. Mammalian cells have four HSF family members involved in dif￾ferent, but in some cases similar, biological functions, including stress resis￾tance, cell differentiation and development. Mammalian HSF family

members exhibit differential specificity for different types of heat shock ele￾ments, which, together with cell type-specific expression of HSFs is impor￾tant in determining the target genes of each HSF. This minireview focuses

on the molecular mechanisms of DNA recognition, chromatin modulation

and gene expression by yeast and mammalian HSFs.

Abbreviations

3P, three perfect repeats; DBD, DNA-binding domain; HDAC1, ; HDAC2, ; HR, hydrophobic heptad repeat; HSE, heat shock element; HSF,

heat shock factor; HSP, heat shock protein; ncRNA, noncoding RNA; PARP, poly(ADP)-ribose polymerase; Pol II, RNA polymerase II;

SAGA, Spt-Ada-Gcn5 acetyltransferase; TFIIA, general transcription factor IIA.

4140 FEBS Journal 277 (2010) 4140–4149 ª 2010 The Authors Journal compilation ª 2010 FEBS