Histone deacetylase 2 (HDAC2) protein-dependent deacetylation of mortality factor 4-like 1 (MORF4L1) protein enhances its homodimerization.

Abstract Histone acetyltransferase mortality factor 4-like 1 (MORF4L1) is a relatively new histone acetyltransferase (HAT) component that exists as a homodimer to exert its epigenetic function. The mechanism of MORF4L1 self-assembly is unknown. Here we report that K148 deacetylation is indispensable for facilitating MORF4L1 self-assembly into a homodimeric unit. Among a stretch of approximately 10 amino acids in the NH2-terminus between the chromodomain and MRG domain within MORF4L1, K148 is normally acetylated. Substitution of K148 with arginine augments MORF4L1 self-assembly. However, acetylation mimics of MORF4L1 including K148L and K148Q abolished its self-assembly of the HAT component. HDAC2, a deacetyltransferase, interacts with and keeps MORF4L1 in a deacetylation status at K148 that triggers MORF4L1 self-assembly. Knockdown of HDAC2 reduces MORF4L1 self-assembly. HDAC2-dependent deacetylation of MORF4L1 enhances MORF4L1 homodimerization thus facilitating functionality of complex formation to repress cell proliferation.