The DNA and protein complex known as chromatin is subject to posttranslational modifications (PTMs) that regulate cellular functions such that PTM dysregulation can lead to disease, including cancer. One critical PTM is acetylation/deacetylation, which is being investigated as a means to develop targeted cancer therapies. The histone acetyltransferase (HAT) family of proteins performs histone acetylation. In humans, MOF (hMOF), a member of the MYST family of HATs, acetylates histone H4 at lysine 16 (H4K16ac). MOF-mediated acetylation plays a critical role in the DNA damage response (DDR) and embryonic stem cell development. Functionally, MOF is found in two distinct complexes: NSL (nonspecific lethal) in humans and MSL (male-specific lethal) in flies. The NSL complex is also able to acetylate additional histone H4 sites. Dysregulation of MOF activity occurs in multiple cancers, including ovarian cancer, medulloblastoma, breast cancer, colorectal cancer, and lung cancer. Bioinformatics analysis of KAT8, the gene encoding hMOF, indicated that it is highly overexpressed in kidney tumors as part of a concerted gene coexpression program that can support high levels of chromosome segregation and cell proliferation. The linkage between MOF and tumor proliferation suggests that there are additional functions of MOF that remain to be discovered.

中文翻译：

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组蛋白乙酰基转移酶MOF在肿瘤发生，DNA损伤反应，增殖和干细胞发育的十字路口协调结果。

称为染色质的DNA和蛋白质复合物会进行翻译后修饰（PTM），该修饰会调节细胞功能，从而PTM失调会导致疾病，包括癌症。一种关键的PTM是乙酰化/脱乙酰化，正在研究它作为开发靶向癌症疗法的一种手段。蛋白的组蛋白乙酰转移酶（HAT）家族可进行组蛋白乙酰化。在人类中，HAT的MYST家族成员MOF（hMOF）在赖氨酸16（H4K16ac）处乙酰化组蛋白H4。MOF介导的乙酰化在DNA损伤反应（DDR）和胚胎干细胞发育中起关键作用。在功能上，MOF存在于两种不同的复合物中：人类中的NSL（非特异性致死性）和果蝇中的MSL（雄性致死性）。NSL复合物还能够乙酰化其他组蛋白H4位点。MOF活性的失调发生在多种癌症中，包括卵巢癌，髓母细胞瘤，乳腺癌，结肠直肠癌和肺癌。生物信息学分析KAT8，编码hMOF基因，表明它在肾肿瘤中高度过表达为能够支持高水平的染色体分离和细胞增殖的协同基因共表达方案的一部分。MOF和肿瘤增殖之间的联系表明，MOF还有其他功能尚待发现。