Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis.
Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcription and cellular homeostasis.
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KAT8的复合物依赖性组蛋白乙酰转移酶活性决定其在转录和细胞内稳态中的作用。
DOI：
10.1016/j.molcel.2021.02.012
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发表时间：
2021-04-15
期刊：
影响因子：
16
通讯作者：
Helin K
中科院分区：
文献类型：
--
作者：
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
组蛋白H4上赖氨酸16（H4K16ac）的乙酰化由组蛋白乙酰转移酶KAT8催化，并可阻止体外染色质致密化。虽然在果蝇中进行了广泛的研究，但H4K16ac和两种含KAT8的蛋白复合物（NSL和MSL）的功能在哺乳动物中还没有得到很好的理解。在这里，我们证明了KAT8的令人惊讶的复合物依赖性活性：它催化H4K5ac和H4K8ac作为NSL复合物的一部分，而它催化H4K16ac作为MSL复合物的一部分。此外，我们表明，MSL复合物蛋白和H4K16ac是不需要细胞增殖和染色质的可及性，而NSL复合物是必不可少的细胞存活，因为它刺激转录起始的启动子管家基因。总之，我们表明，KAT8开关催化活性和功能取决于其相关的蛋白质，并且，当在NSL复合物中时，它催化必需基因表达所需的H4K5ac和H4K8ac。Radzisheuskaya等人报道了组蛋白乙酰转移酶KAT8根据相关蛋白质转换功能。它催化启动子相关的H4K5和H4K8乙酰化，作为NSL复合物的一部分，这是激活必需基因所必需的。作为MSL复合物的一部分，它将H4K16乙酰化标记所有开放的染色质。
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. 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.
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影响因子：
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