Details

Autor(en) / Beteiligte

• Radzisheuskaya, Aliaksandra
• Shliaha, Pavel V.
• Grinev, Vasily V.
• Shlyueva, Daria
• Damhofer, Helene
• Koche, Richard
• Gorshkov, Vladimir
• Kovalchuk, Sergey
• Zhan, Yingqian
• Rodriguez, Keli L.
• Johnstone, Andrea L.
• Keogh, Michael-C
• Hendrickson, Ronald C.
• Jensen, Ole N.
• Helin, Kristian

Titel

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

Ist Teil von

• Molecular cell, 2021-04, Vol.81 (8), p.1749-1765.e8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• 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. [Display omitted] •The NSL but not the MSL complex is essential for the proliferation of human cells•The NSL complex places H4K5ac and H4K8ac at TSSs, promoting transcription initiation•H4K16ac is a highly abundant modification placed by KAT8 as part of the MSL complex•H4K16ac marks open chromatin but does not affect global chromatin accessibility Radzisheuskaya et al. report that histone acetyltransferase KAT8 switches functions depending on associated proteins. It catalyzes promoter-associated H4K5 and H4K8 acetylation as part of the NSL complex, which is required for the activation of essential genes. As part of the MSL complex, it places H4K16 acetylation marking all open chromatin.