title: A dual role for SAGA-associated factor 29 (SGF29) in ER stress survival by coordination of both histone H3 acetylation and histone H3 lysine-4 trimethylation.
abstract: The SGF29 protein binds to tri-methylated lysine-4 of histone H3 (H3K4me3), which is a histone modification associated with active promoters. Human SGF29 is a subunit of the histone acetyltransferase module of the SAGA (Spt-Ada-Gcn5 acetyltransferase) and ATAC (Ada-Two-A-containing 2A) co-activator complexes. Previous work revealed that the SAGA complex is recruited to endoplasmic reticulum (ER) stress target genes and required for their induction. Here, we report the involvement of SGF29 in the survival of human cells from ER stress. SGF29 knockdown results in impaired transcription of the ER stress genes GRP78 and CHOP. Besides histone H3K14 acetylation, we find that SGF29 is also required for the maintenance of H3K4me3 at these genes, which is already present prior to ER stress. Reduced levels of H3K4me3 in the absence of SGF29 correlate with a decreased association of ASH2L, which is a core component of the SET1/MLL complexes, to GFP78 and CHOP. In conclusion, our results suggest that the H3K4me3-binding protein SGF29 plays a central and dual role in the ER stress response. Prior to ER stress, the protein coordinates H3K4me3 levels, thereby maintaining a 'poised' chromatin state on ER stress target gene promoters. Following ER stress induction, SGF29 is required for increased H3K14 acetylation on these genes, which then results in full transcriptional activation, thereby promoting cell survival.
authors.affiliation: Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Andrea W
authors.initials: AW
authors.lastname: Schram
authors.forename: Roy
authors.initials: R
authors.lastname: Baas
authors.forename: Pascal W T C
authors.initials: PW
authors.lastname: Jansen
authors.forename: Anne
authors.initials: A
authors.lastname: Riss
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tora
authors.forename: Michiel
authors.initials: M
authors.lastname: Vermeulen
authors.forename: H Th Marc
authors.initials: HT
authors.lastname: Timmers
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D051742:Transcription Factor CHOP / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006657:Histones; D051742:Transcription Factor CHOP; D000123:Acetyltransferases; C561317:Sgf29 protein, human; D008239:Lysine
references.citation: Int J Cell Biol. 2010;2010:830307
references.pmid: 20169136
references.citation: J Biol Chem. 1999 Feb 26;274(9):5895-900
references.pmid: 10026213
references.citation: J Proteome Res. 2011 Apr 1;10(4):1794-805
references.pmid: 21254760
references.citation: Cell. 1998 Aug 7;94(3):363-74
references.pmid: 9708738
references.citation: Mol Syst Biol. 2011 Jul 05;7:503
references.pmid: 21734642
references.citation: BMC Genomics. 2012 Aug 24;13:424
references.pmid: 22920947
references.citation: Pharmacol Ther. 2012 Jun;134(3):306-16
references.pmid: 22387231
references.citation: Mol Cell. 2007 Jan 12;25(1):15-30
references.pmid: 17218268
references.citation: Cell. 1996 Mar 22;84(6):843-51
references.pmid: 8601308
references.citation: Nucleic Acids Res. 2006 Jun 06;34(10):3116-27
references.pmid: 16757577
references.citation: Genes Dev. 1997 Jul 1;11(13):1640-50
references.pmid: 9224714
references.citation: Cell Death Dis. 2012 Nov 22;3:e429
references.pmid: 23171849
references.citation: Science. 2001 Jun 22;292(5525):2333-7
references.pmid: 11423663
references.citation: Mol Cell. 2011 Apr 8;42(1):118-26
references.pmid: 21474073
references.citation: Cell Mol Life Sci. 2010 Feb;67(4):611-28
references.pmid: 19936620
references.citation: Cell. 2010 Sep 17;142(6):967-80
references.pmid: 20850016
references.citation: Nature. 2007 Aug 2;448(7153):553-60
references.pmid: 17603471
references.citation: Epigenomics. 2010 Jun;2(3):395-406
references.pmid: 22121900
references.citation: Genes Dev. 2002 Mar 15;16(6):673-5
references.pmid: 11963920
references.citation: Cell. 2013 Feb 28;152(5):1021-36
references.pmid: 23452851
references.citation: Mol Cell. 2013 Jan 24;49(2):368-78
references.pmid: 23201125
references.citation: Genes Dev. 2012 Mar 15;26(6):527-41
references.pmid: 22426530
references.citation: Curr Opin Struct Biol. 2011 Dec;21(6):767-74
references.pmid: 22014650
references.citation: Mol Cell. 2011 Nov 4;44(3):410-423
references.pmid: 22055187
references.citation: Curr Opin Cell Biol. 2008 Jun;20(3):341-8
references.pmid: 18508253
references.citation: Mol Cell. 2009 Jan 30;33(2):248-56
references.pmid: 19187765
references.citation: Biochemistry. 2012 Jan 17;51(2):706-14
references.pmid: 22224423
references.citation: Nature. 2006 Jul 6;442(7098):91-5
references.pmid: 16728978
references.citation: Gene. 2012 Apr 1;496(2):69-78
references.pmid: 22285924
references.citation: J Biol Chem. 2012 Jun 29;287(27):23035-45
references.pmid: 22577136
references.citation: Nat Rev Mol Cell Biol. 2006 Sep;7(9):657-66
references.pmid: 16912715
references.citation: Nature. 2011 May 5;473(7345):43-9
references.pmid: 21441907
references.citation: Cell. 2007 Oct 5;131(1):58-69
references.pmid: 17884155
references.citation: J Biol Chem. 2007 May 4;282(18):13419-28
references.pmid: 17355966
references.citation: Crit Rev Biochem Mol Biol. 2010 Dec;45(6):488-505
references.pmid: 20923397
references.citation: J Biol Chem. 1990 Dec 15;265(35):22029-34
references.pmid: 2254345
references.citation: Mol Cell Biol. 2009 Mar;29(6):1649-60
references.pmid: 19114550
references.citation: J Cell Biol. 2008 Jun 16;181(6):893-901
references.pmid: 18541701
references.citation: EMBO J. 2010 Dec 1;29(23):3967-78
references.pmid: 20953165
references.citation: Mol Cell Biol. 1999 Jan;19(1):86-98
references.pmid: 9858534
references.citation: Nat Cell Biol. 2004 Jan;6(1):73-7
references.pmid: 14661024
references.citation: Mol Cell. 2004 Feb 27;13(4):573-85
references.pmid: 14992726
references.citation: EMBO J. 2011 Jun 17;30(14):2829-42
references.pmid: 21685874
references.citation: Cell. 2005 Jan 28;120(2):169-81
references.pmid: 15680324
references.citation: Nat Rev Mol Cell Biol. 2007 Jul;8(7):519-29
references.pmid: 17565364
references.citation: Nat Rev Mol Cell Biol. 2005 Nov;6(11):838-49
references.pmid: 16261189
references.citation: Nature. 2006 Jul 6;442(7098):86-90
references.pmid: 16728976