Histone deacetylase 2 (HDAC2) protein-dependent deacetylation of mortality factor 4-like 1 (MORF4L1) protein enhances its homodimerization.
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.
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. Electronic address: chenyan99727@163.com.
Yan
Y
Chen
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.
Jin
J
Li
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.
Sarah
S
Dunn
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.
Sheng
S
Xiong
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.
Wei
W
Chen
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania 15240.
Yutong
Y
Zhao
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania 15240.
Bill B
BB
Chen
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania 15240.
Rama K
RK
Mallampalli
Department of Medicine, Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania 15213. Electronic address: zouc@upmc.edu.
Chunbin
C
Zou
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D056464:Histone Deacetylase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017384:Sequence Deletion; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; C471162:MRG15 protein, mouse; D015534:Trans-Activators; D001120:Arginine; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2
Epigenetics; Histone Acetylase; Histone Deacetylase; Posttranslational Modification; Proliferation; Protein Complexes; Protein Structure; Site-directed Mutagenesis