Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis Journal Article

   

Authors:	Radzisheuskaya, A.; Shliaha, P. V.; Grinev, V. V.; Shlyueva, D.; Damhofer, H.; Koche, R.; Gorshkov, V.; Kovalchuk, S.; Zhan, Y.; Rodriguez, K. L.; Johnstone, A. L.; Keogh, M. C.; Hendrickson, R. C.; Jensen, O. N.; Helin, K.
Article Title:	Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis
Abstract:	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. © 2021 Elsevier Inc.
Keywords:	controlled study; unclassified drug; human cell; promoter region; nonhuman; flow cytometry; protein function; cell proliferation; animal cell; mouse; cell survival; gene expression; transcription initiation; animal experiment; protein; transcription factor; chromatin; transcription; real time polymerase chain reaction; catalysis; cell metabolism; rna extraction; mammal cell; housekeeping gene; histone acetyltransferase; histone acetylation; guide rna; essential gene; human; male; female; article; hek293 cell line; hela cell line; wdr5 protein; thp-1 cell line; u2os cell line; molm-13 cell line; k-562 cell line; h4k16ac; h4k5ac; h4k8ac; kat8; msl complex; nsl complex; acetylation of lysine 5 on histone h4; acetylation of lysine 8 on histone h4; ddx21 protein; gtf3c3 protein; h4k12ack16ac protein; h4k5ack12ack16ac protein; h4k5ack16ac protein; h4k8ack12ack16ac protein; h4k8ack16ac protein; hcfc1 protein; histone acetyltransferase kat8; hspa5 protein; isy1 protein; kansl1 protein; kansl2 protein; kansl3 protein; lars2 protein; magoh protein; malsu1 protein; mcrs1 protein; mrpl9 protein; mrps31 protein; msl1 protein; msl2 protein; msl3 protein; ogt protein; phf20 protein; phf20l1 protein; pmpcb protein; pop4 protein; ppm1g protein; qrsl1 protein; rpap1 protein; rrp15 protein; slc25a26 protein; tars2 protein; tefm protein; ttc27 protein; caki-1 cell line
Journal Title:	Molecular Cell
Volume:	81
Issue:	8
ISSN:	1097-2765
Publisher:	Cell Press
Date Published:	2021-04-15
Start Page:	1749
End Page:	1765.e8
Language:	English
DOI:	10.1016/j.molcel.2021.02.012
PUBMED:	33657400
PROVIDER:	scopus
PMCID:	PMC8056186
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85103297674&doi=10.1016%2fj.molcel.2021.02.012&partnerID=40&md5=186e6c75104b6d9e2226f16ccfde098a
Notes:	Article -- Export Date: 3 May 2021 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/180160