title: Transcriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells.
abstract: Heat shock factors (HSFs) are the master regulators of transcription under protein-damaging conditions, acting in an environment where the overall transcription is silenced. We determined the genomewide transcriptional program that is rapidly provoked by HSF1 and HSF2 under acute stress in human cells. Our results revealed the molecular mechanisms that maintain cellular homeostasis, including HSF1-driven induction of polyubiquitin genes, as well as HSF1- and HSF2-mediated expression patterns of cochaperones, transcriptional regulators, and signaling molecules. We characterized the genomewide transcriptional response to stress also in mitotic cells where the chromatin is tightly compacted. We found a radically limited binding and transactivating capacity of HSF1, leaving mitotic cells highly susceptible to proteotoxicity. In contrast, HSF2 occupied hundreds of loci in the mitotic cells and localized to the condensed chromatin also in meiosis. These results highlight the importance of the cell cycle phase in transcriptional responses and identify the specific mechanisms for HSF1 and HSF2 in transcriptional orchestration. Moreover, we propose that HSF2 is an epigenetic regulator directing transcription throughout cell cycle progression.
authors: Department of Biosciences, Åbo Akademi University, 20520 Turku, Finland.
authors: Anniina
authors: A
authors: Vihervaara
authors: Christian
authors: C
authors: Sergelius
authors: Jenni
authors: J
authors: Vasara
authors: Malin A H
authors: MA
authors: Blom
authors: Alexandra N
authors: AN
authors: Elsing
authors: Pia
authors: P
authors: Roos-Mattjus
authors: Lea
authors: L
authors: Sistonen
mesh_terms: D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics*; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D008297:Male; D008938:Mitosis / Q000235:genetics*; D018832:Molecular Chaperones / Q000235:genetics; D025821:Polyubiquitin / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D014157:Transcription Factors; D025821:Polyubiquitin; C070389:HSF2 protein, human
keywords: ChIP-seq; ENCODE; human genome; proteostasis
references: EMBO J. 2004 Oct 27;23(21):4297-306
references: 15483628
references: Annu Rev Biochem. 2011;80:1089-115
references: 21417720
references: J Biochem. 2010 Jun;147(6):793-8
references: 20418328
references: J Biol Chem. 2010 Nov 5;285(45):34469-76
references: 20802198
references: Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):602-7
references: 16407123
references: J Biol Chem. 2007 Mar 9;282(10):7077-86
references: 17213196
references: J Cell Sci. 2003 May 15;116(Pt 10):1991-2003
references: 12679384
references: Int J Androl. 2007 Apr;30(2):80-7
references: 17014532
references: PLoS One. 2011 Jan 14;6(1):e15934
references: 21264254
references: Cell. 2012 Aug 3;150(3):549-62
references: 22863008
references: Curr Biol. 2006 Jul 25;16(14):1414-21
references: 16860740
references: EMBO J. 1997 May 1;16(9):2452-62
references: 9171358
references: Nature. 2011 Jul 20;475(7356):324-32
references: 21776078
references: FEBS Lett. 1999 Nov 12;461(1-2):125-9
references: 10561509
references: Mol Cell Biol. 1993 Mar;13(3):1392-407
references: 8441385
references: Bioinformatics. 2011 Jun 15;27(12):1696-7
references: 21486936
references: Cell. 1988 Sep 9;54(6):795-804
references: 3136931
references: EMBO J. 2012 Nov 5;31(21):4221-35
references: 22990239
references: Mol Cell. 2010 Feb 12;37(3):344-54
references: 20159554
references: Genome Biol. 2009;10(3):R25
references: 19261174
references: EMBO J. 2002 Jun 3;21(11):2591-601
references: 12032072
references: J Cell Sci. 2008 Aug 1;121(Pt 15):2540-54
references: 18628300
references: Ann N Y Acad Sci. 1960 Oct 7;90:409-21
references: 13775619
references: Nat Protoc. 2012 Sep;7(9):1728-40
references: 22936215
references: J Cell Biochem. 2008 Sep 1;105(1):1-8
references: 18459122
references: Nat Rev Mol Cell Biol. 2010 Aug;11(8):579-92
references: 20651708
references: Mol Cell Biol. 2006 Feb;26(3):955-64
references: 16428449
references: J Biol Chem. 2005 Oct 14;280(41):34908-16
references: 16051598
references: Nature. 1984 Sep 6-11;311(5981):81-4
references: 6472466
references: Mol Cell Biol. 2010 Dec;30(24):5608-20
references: 20937767
references: Genes Dev. 2006 Apr 1;20(7):836-47
references: 16600913
references: Cell Death Differ. 2006 Feb;13(2):212-22
references: 16151457
references: Nature. 1992 Oct 15;359(6396):644-7
references: 1406996
references: Nat Rev Genet. 2009 Oct;10(10):669-80
references: 19736561
references: Genes Dev. 2007 Oct 1;21(19):2385-98
references: 17908926
references: Mol Cell Biol. 2004 Jun;24(12):5249-56
references: 15169889
references: Nat Rev Mol Cell Biol. 2009 Mar;10(3):192-206
references: 19234478
references: Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18378-83
references: 22042860
references: Biochim Biophys Acta. 2012 Mar;1823(3):624-35
references: 21951723
references: Cell. 2007 Sep 21;130(6):1005-18
references: 17889646
references: Mol Biol Cell. 2011 Oct;22(19):3571-83
references: 21813737
references: Mol Cell Biol. 1988 Nov;8(11):4727-35
references: 2463465
references: Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11224-9
references: 18682557
references: Cold Spring Harb Symp Quant Biol. 2010;75:1-9
references: 21467139
references: J Biol Chem. 2006 Feb 24;281(8):4931-7
references: 16306048
references: Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7923-7
references: 8367444
references: Genome Biol. 2003;4(5):P3
references: 12734009
references: Cell Stress Chaperones. 2009 Jan;14(1):105-11
references: 18663603
references: Cell Stress Chaperones. 2007 Autumn;12(3):283-90
references: 17915561
references: Nat Rev Mol Cell Biol. 2010 Aug;11(8):545-55
references: 20628411
references: Biochem J. 2006 Apr 1;395(1):223-31
references: 16336210
references: J Biol Chem. 1998 Sep 25;273(39):25466-71
references: 9738016
references: Mol Cell. 2007 Jul 6;27(1):107-19
references: 17612494
references: Mol Cell Biol. 1993 Jun;13(6):3370-83
references: 8497256
references: FEBS J. 2010 Oct;277(20):4126-39
references: 20945529
references: PLoS Genet. 2010 Sep 09;6(9):e1001114
references: 20844575
references: Mol Cell. 2009 Dec 25;36(6):970-83
references: 20064463
references: Nat Rev Mol Cell Biol. 2012 Feb 23;13(3):153-67
references: 22358331
references: Mol Cell. 2010 Feb 12;37(3):355-69
references: 20159555
references: Mol Cell Biol. 2000 Jun;20(12):4188-98
references: 10825184
references: Nat Rev Genet. 2012 Oct;13(10):720-31
references: 22986266
references: Nature. 2006 Apr 20;440(7087):1013-7
references: 16625188
references: Nat Methods. 2009 Nov;6(11 Suppl):S22-32
references: 19844228
references: Nat Biotechnol. 2011 Jan;29(1):24-6
references: 21221095
references: Mol Cell. 2012 Oct 26;48(2):182-94
references: 22940245
references: Nature. 1995 Mar 9;374(6518):126
references: 7877683
references: Science. 2005 Jan 21;307(5708):421-3
references: 15662014
references: Mol Biol Cell. 2005 Aug;16(8):3776-85
references: 15930131
references: Science. 2007 Jun 8;316(5830):1497-502
references: 17540862
references: Nat Struct Mol Biol. 2005 Oct;12(10):935-6
references: 16155580
references: Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5367-72
references: 18391197
references: Mol Cell Biol. 1992 Sep;12(9):4104-11
references: 1508207
references: PLoS Biol. 2011 Apr;9(4):e1001046
references: 21526222
references: Nature. 2006 Aug 31;442(7106):1050-3
references: 16929308
references: Cell Rep. 2012 Oct 25;2(4):1025-35
references: 23062713
references: Mol Biol Cell. 2004 Mar;15(3):1254-61
references: 14668476
references: J Biol Chem. 1998 Mar 27;273(13):7523-8
references: 9516453
references: Cell. 1995 Oct 6;83(1):29-38
references: 7553870
references: Nat Methods. 2012 Jul;9(7):671-5
references: 22930834
references: Mol Biol Cell. 2009 Mar;20(5):1340-7
references: 19129477
references: EMBO J. 2003 Jul 15;22(14):3737-48
references: 12853488
references: Mol Cell. 2010 Oct 22;40(2):253-66
references: 20965420
references: Cell. 2007 Sep 21;130(6):986-8
references: 17889643
references: Cell. 2012 Aug 31;150(5):987-1001
references: 22939624
references: EMBO J. 2011 May 17;30(13):2520-31
references: 21587205