Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis.
Acetylation
Animals
Cell Line
Cell Line, Tumor
Cell Nucleus
/ genetics
Cell Proliferation
/ genetics
Chromatin
/ genetics
HEK293 Cells
HeLa Cells
Histone Acetyltransferases
/ genetics
Histones
/ genetics
Homeostasis
/ genetics
Humans
K562 Cells
Lysine
/ genetics
Male
Mice
Promoter Regions, Genetic
/ genetics
THP-1 Cells
Transcription, Genetic
/ genetics
H4K16ac
H4K5ac
H4K8ac
KAT8
MSL complex
NSL complex
chromatin
histone acetylation
transcription
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
15 04 2021
15 04 2021
Historique:
received:
13
10
2020
revised:
01
02
2021
accepted:
04
02
2021
pubmed:
4
3
2021
medline:
30
4
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
Acetylation of lysine 16 on histone H4 (H4K16ac) is catalyzed by histone acetyltransferase KAT8 and can prevent chromatin compaction in vitro. Although extensively studied in Drosophila, the functions of H4K16ac and two KAT8-containing protein complexes (NSL and MSL) are not well understood in mammals. Here, we demonstrate a surprising complex-dependent activity of KAT8: it catalyzes H4K5ac and H4K8ac as part of the NSL complex, whereas it catalyzes the bulk of H4K16ac as part of the MSL complex. Furthermore, we show that MSL complex proteins and H4K16ac are not required for cell proliferation and chromatin accessibility, whereas the NSL complex is essential for cell survival, as it stimulates transcription initiation at the promoters of housekeeping genes. In summary, we show that KAT8 switches catalytic activity and function depending on its associated proteins and that, when in the NSL complex, it catalyzes H4K5ac and H4K8ac required for the expression of essential genes.
Identifiants
pubmed: 33657400
pii: S1097-2765(21)00098-8
doi: 10.1016/j.molcel.2021.02.012
pmc: PMC8056186
mid: NIHMS1674320
pii:
doi:
Substances chimiques
Chromatin
0
Histones
0
Histone Acetyltransferases
EC 2.3.1.48
KAT8 protein, human
EC 2.3.1.48
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1749-1765.e8Subventions
Organisme : NIGMS NIH HHS
ID : R44 GM136172
Pays : United States
Organisme : NIGMS NIH HHS
ID : R44 GM116584
Pays : United States
Organisme : NCI NIH HHS
ID : R44 CA212733
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NHGRI NIH HHS
ID : R44 HG008907
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests EpiCypher is a commercial developer and supplier of reagents (recombinant semi-synthetic modified nucleosomes) and the antibody characterization platforms used in this study. K.H. is a consultant for Inthera Bioscience AG and a scientific advisor for Hannibal Health Innovation.
Références
Biophys J. 2017 Feb 7;112(3):450-459
pubmed: 27931745
Mol Cell. 2009 Oct 23;36(2):290-301
pubmed: 19854137
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Mol Cell. 2010 Jun 25;38(6):827-41
pubmed: 20620954
PLoS Genet. 2013 Nov;9(11):e1003940
pubmed: 24244196
Nucleic Acids Res. 2018 Jan 4;46(D1):D754-D761
pubmed: 29155950
Nucleic Acids Res. 2016 Jan 4;44(D1):D717-25
pubmed: 26590259
Oncol Rep. 2015 Feb;33(2):685-92
pubmed: 25483274
J Mol Biol. 2012 Aug 3;421(1):30-7
pubmed: 22575889
Science. 2009 Oct 9;326(5950):289-93
pubmed: 19815776
Anal Chem. 2006 Nov 15;78(22):7796-801
pubmed: 17105173
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Int J Cancer. 2008 Mar 15;122(6):1207-13
pubmed: 18058815
Science. 2000 May 26;288(5470):1422-5
pubmed: 10827952
Nat Struct Mol Biol. 2019 Nov;26(11):999-1012
pubmed: 31611688
Nucleic Acids Res. 2013 Jan;41(Database issue):D1063-9
pubmed: 23203882
Nat Genet. 2005 Apr;37(4):391-400
pubmed: 15765097
Nat Commun. 2018 Jan 15;9(1):189
pubmed: 29335486
Nat Struct Mol Biol. 2019 Oct;26(10):870-879
pubmed: 31582847
Development. 2017 Jun 15;144(12):2165-2174
pubmed: 28506985
Nature. 2011 Mar 3;471(7336):115-8
pubmed: 21368835
Mol Cell Proteomics. 2019 Feb;18(2):383-390
pubmed: 30373789
Mol Cell Proteomics. 2015 Apr;14(4):1148-58
pubmed: 25680960
Cell. 2016 Oct 20;167(3):722-738.e23
pubmed: 27768893
Mol Cell Proteomics. 2015 Jun;14(6):1696-707
pubmed: 25805797
Bioinformatics. 2014 Sep 1;30(17):2524-6
pubmed: 24794931
EMBO Rep. 2019 Jul;20(7):e47630
pubmed: 31267707
Cell Stem Cell. 2012 Aug 3;11(2):163-78
pubmed: 22862943
J Biol Chem. 2010 Feb 12;285(7):4268-72
pubmed: 20018852
Mol Cell. 2017 Jul 6;67(1):5-18.e19
pubmed: 28673542
Anal Chem. 2015 Nov 17;87(22):11448-54
pubmed: 26505526
Genetics. 1980 Sep;96(1):165-86
pubmed: 6781985
Mol Cell Biol. 2008 Aug;28(16):5093-105
pubmed: 18541669
Nucleic Acids Res. 2015 Aug 18;43(14):6959-68
pubmed: 26117547
Nucleic Acids Res. 2013 May 1;41(10):e108
pubmed: 23558742
Cell. 2019 Oct 3;179(2):470-484.e21
pubmed: 31543265
EMBO J. 1997 Apr 15;16(8):2054-60
pubmed: 9155031
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Nat Protoc. 2013 Sep;8(9):1765-86
pubmed: 23975260
Cell. 2013 Feb 28;152(5):1021-36
pubmed: 23452851
Nat Commun. 2020 Jul 29;11(1):3696
pubmed: 32728046
Elife. 2014 Jun 04;3:
pubmed: 24898753
Epigenetics Chromatin. 2010 Oct 20;3(1):18
pubmed: 20961410
Nucleic Acids Res. 2011 Mar;39(5):1680-91
pubmed: 21047799
Biochim Biophys Acta. 2016 Mar;1859(3):462-7
pubmed: 26455954
J Mol Biol. 2011 Dec 16;414(5):749-64
pubmed: 22051513
Nat Cell Biol. 2019 Oct;21(10):1248-1260
pubmed: 31576060
Genetics. 1976 Oct;84(2):257-66
pubmed: 826446
Mol Cell. 2000 Feb;5(2):367-75
pubmed: 10882077
Nat Biotechnol. 2010 Aug;28(8):817-25
pubmed: 20657582
Genome Res. 2009 Sep;19(9):1639-45
pubmed: 19541911
Nature. 2013 Aug 22;500(7463):468-71
pubmed: 23863932
Front Med. 2014 Mar;8(1):79-83
pubmed: 24452550
Nucleic Acids Res. 2016 Oct 14;44(18):e141
pubmed: 27353328
Nat Chem Biol. 2018 May;14(5):431-441
pubmed: 29581585
Genome Res. 2018 Nov;28(11):1688-1700
pubmed: 30279224
Bioinformatics. 2009 Oct 1;25(19):2607-8
pubmed: 19654119
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Nucleic Acids Res. 2019 May 7;47(8):e47
pubmed: 30783653
Genes Cells. 1998 Dec;3(12):789-800
pubmed: 10096020
Cold Spring Harb Perspect Biol. 2015 May 01;7(5):
pubmed: 25934013
PLoS Genet. 2012;8(6):e1002736
pubmed: 22723752
Int J Oncol. 2014 Apr;44(4):1207-14
pubmed: 24452485
Genome Biol. 2014 Feb 03;15(2):R29
pubmed: 24485249
Mol Cell. 2006 Mar 17;21(6):811-23
pubmed: 16543150
Genome Res. 2013 Dec;23(12):2053-65
pubmed: 23990607
Nat Commun. 2020 May 7;11(1):2243
pubmed: 32382029
J Mol Biol. 2008 Sep 12;381(4):816-25
pubmed: 18653199
Nucleic Acids Res. 2012 Feb;40(4):1509-22
pubmed: 22039099
Oncogene. 2016 May;35(21):2698-710
pubmed: 26387537
Oncol Lett. 2013 Aug;6(2):393-400
pubmed: 24137335
Nature. 2011 May 5;473(7345):43-9
pubmed: 21441907
Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):13336-13341
pubmed: 30530664
Biochem Biophys Res Commun. 2014 Sep 26;452(3):575-80
pubmed: 25181338
Nat Methods. 2017 Oct;14(10):959-962
pubmed: 28846090
Elife. 2014 May 19;3:e02024
pubmed: 24842875
J Vis Exp. 2016 May 17;(111):
pubmed: 27286567
Genome Biol. 2015 Dec 01;16:259
pubmed: 26619908
Genes Dev. 2019 Apr 1;33(7-8):452-465
pubmed: 30819819
Science. 2006 Feb 10;311(5762):844-7
pubmed: 16469925
Cell. 2012 Mar 30;149(1):214-31
pubmed: 22464331
Nat Methods. 2012 Oct;9(10):999-1003
pubmed: 22941365
Nat Struct Mol Biol. 2016 Apr;23(4):349-57
pubmed: 26926434
Cell Stem Cell. 2020 Sep 3;27(3):441-458.e10
pubmed: 32610040
Mol Cell Biol. 2010 Jul;30(14):3582-95
pubmed: 20479123
Mol Cell Biol. 2008 Jan;28(1):397-409
pubmed: 17967868
Science. 2018 May 18;360(6390):800-805
pubmed: 29622725