PXD022267-1

PXD022267 is an original dataset announced via ProteomeXchange.

Title	Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcriptional regulation and cellular homeostasis [AP-MS]
Description	Histone acetylation is associated with open chromatin and transcriptionally active genes. Specifically, acetylation of lysine 16 on histone H4 (H4K16ac) has been shown to prevent the assembly of nucleosomal arrays in vitro. This modification is catalyzed by the MYST-family histone acetyltransferase KAT8 (also known as MOF and MYST1), which is part of two distinct chromatin-associated complexes: NSL and MSL. While extensively studied in Drosophila, the functions of H4K16ac and the two KAT8-containing complexes in mammalian cells are not well understood. Here, we demonstrate a surprising complex-dependent activity of KAT8. We found that KAT8 catalyzes H4K5 and H4K8 acetylation as part of the NSL complex, whereas it catalyzes the bulk of H4K16 acetylation as part of the MSL complex. Furthermore, we show that the core proteins of the MSL complex and H4K16ac are not required for cell proliferation and global chromatin accessibility, whereas the NSL complex is essential for cell survival, as it is enriched at the promoters of housekeeping genes and is required for their transcription initiation. In summary, we show that KAT8 switches catalytic activity and function depending on its associated proteins, and that, as part of the NSL complex, it catalyzes H4K5 and H4K8 acetylation required for the expression of genes essential for cell survival
HostingRepository	PRIDE
AnnounceDate	2021-06-29
AnnouncementXML	Submission_2021-06-29_10:17:16.629.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Shliaha
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-30 04:15:11	ID requested
⏵ 1	2021-06-29 10:17:17	announced

Radzisheuskaya A, Shliaha PV, Grinev VV, Shlyueva D, Damhofer H, Koche R, Gorshkov V, Kovalchuk S, Zhan Y, Rodriguez KL, Johnstone AL, Keogh MC, Hendrickson RC, Jensen ON, Helin K, Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis. Mol Cell, 81(8):1749-1765.e8(2021) [pubmed]

submitter keyword: histone, MSL, NSL, KAT8

Ole N Jensen
contact affiliation	University of Southern Denmark, Department of Biochemistryand Molecular Biology, Protein Research Group (lab head)
contact email	jenseno@bmb.sdu.dk
lab head
Pavel Shliaha
contact affiliation	Syddansk University
contact email	pavels@bmb.sdu.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022267
     1. Label: PRIDE project
     2. Name: Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcriptional regulation and cellular homeostasis [AP-MS]