Laboratory of Chromatin Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):13336-13341. doi: 10.1073/pnas.1817274115. Epub 2018 Dec 10.
Acetylation of histone H4 at lysine 16 (H4K16) modulates nucleosome-nucleosome interactions and directly affects nucleosome binding by certain proteins. In , H4K16 acetylation by the dosage compensation complex subunit Mof is linked to increased transcription of genes on the single X chromosome in males. Here, we analyzed containing different H4K16 mutations or lacking Mof protein. An H4K16A mutation causes embryonic lethality in both sexes, whereas an H4K16R mutation permits females to develop into adults but causes lethality in males. The acetyl-mimic mutation H4K16Q permits both females and males to develop into adults. Complementary analyses reveal that males lacking maternally deposited and zygotically expressed Mof protein arrest development during gastrulation, whereas females of the same genotype develop into adults. Together, this demonstrates the causative role of H4K16 acetylation by Mof for dosage compensation in and uncovers a previously unrecognized requirement for this process already during the onset of zygotic gene transcription.
组蛋白 H4 赖氨酸 16 的乙酰化（H4K16）调节核小体-核小体相互作用，并直接影响某些蛋白质与核小体的结合。在 中，雄性个体中剂量补偿复合物亚基 Mof 介导的 H4K16 乙酰化与单条 X 染色体上基因转录的增加有关。在这里，我们分析了含有不同 H4K16 突变或缺乏 Mof 蛋白的 。H4K16A 突变导致雌雄个体均出现胚胎致死，而 H4K16R 突变使雌性个体发育为成体，但导致雄性个体致死。乙酰化模拟突变 H4K16Q 使雌性和雄性个体均发育为成体。补充分析表明，缺乏母体沉积和合子表达的 Mof 蛋白的雄性个体在原肠胚形成期间停止发育，而具有相同基因型的雌性个体发育为成体。总之，这证明了 Mof 对 H4K16 乙酰化在 中的剂量补偿的因果作用，并揭示了在合子基因转录开始时就存在这一过程的先前未被认识到的需求。
