Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Department of Respiratory Medicine, The Second Xiangya Hospital, Central-South University, Changsha, Hunan 410011, China.
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.
J Biol Chem. 2014 Mar 7;289(10):7092-7098. doi: 10.1074/jbc.M113.527507. Epub 2014 Jan 22.
Histone acetyltransferase mortality factor 4-like 1 (MORF4L1) is a relatively new histone acetyltransferase component that exists as a homodimer to exert its epigenetic function. The mechanism of MORF4L1 self-assembly is unknown. Here we report that Lys-148 deacetylation is indispensable for facilitating MORF4L1 self-assembly into a homodimeric unit. Among a stretch of ∼10 amino acids in the NH2 terminus between the chromodomain and MORF4-related gene (MRG) domain within MORF4L1, Lys-148 is normally acetylated. Substitution of Lys-148 with arginine augments MORF4L1 self-assembly. However, acetylation mimics of MORF4L1, including K148L and K148Q, abolished its self-assembly of the histone acetyltransferase component. HDAC2, a deacetylase, interacts with and keeps MORF4L1 in a deacetylation status at Lys(148) that triggers MORF4L1 self-assembly. Knockdown of HDAC2 reduces MORF4L1 self-assembly. HDAC2-dependent deacetylation of MORF4L1 enhances MORF4L1 homodimerization, thus facilitating the functionality of complex formation to repress cell proliferation.
组蛋白乙酰转移酶死亡因子 4 样蛋白 1（MORF4L1）是一种相对较新的组蛋白乙酰转移酶成分，以同源二聚体的形式存在以发挥其表观遗传功能。MORF4L1 自我组装的机制尚不清楚。在这里，我们报告说赖氨酸 148 的去乙酰化对于促进 MORF4L1 自组装成同源二聚体单位是必不可少的。在 MORF4L1 中的色氨酸结构域和 MORF4 相关基因 (MRG) 结构域之间的 NH2 末端的约 10 个氨基酸的一段中，赖氨酸 148 通常被乙酰化。赖氨酸 148 被精氨酸取代会增强 MORF4L1 的自我组装。然而，MORF4L1 的乙酰化模拟物，包括 K148L 和 K148Q，消除了其组蛋白乙酰转移酶成分的自我组装。去乙酰化酶 HDAC2 与 MORF4L1 相互作用，并使其保持在赖氨酸 148 的去乙酰化状态，从而触发 MORF4L1 的自我组装。HDAC2 的敲低会减少 MORF4L1 的自我组装。MORF4L1 依赖于 HDAC2 的去乙酰化增强了 MORF4L1 同源二聚化，从而促进了复合物形成的功能，以抑制细胞增殖。
