title: ALKBH4-dependent demethylation of actin regulates actomyosin dynamics.
abstract: Regulation of actomyosin dynamics by post-transcriptional modifications in cytoplasmic actin is still poorly understood. Here we demonstrate that dioxygenase ALKBH4-mediated demethylation of a monomethylated site in actin (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes such as cytokinesis and cell migration. ALKBH4-deficient cells display elevated K84me1 levels. Non-muscle myosin II only interacts with unmethylated actin and its proper recruitment to and interaction with actin depend on ALKBH4. ALKBH4 co-localizes with the actomyosin-based contractile ring and midbody via association with methylated actin. ALKBH4-mediated regulation of actomyosin dynamics is completely dependent on its catalytic activity. Disorganization of cleavage furrow components and multinucleation associated with ALKBH4 deficiency can all be restored by reconstitution with wild-type but not catalytically inactive ALKBH4. Similar to actin and myosin knock-out mice, homozygous Alkbh4 mutant mice display early embryonic lethality. These findings imply that ALKBH4-dependent actin demethylation regulates actomyosin function by promoting actin-non-muscle myosin II interaction.
authors.affiliation: Genome Structure and Stability Group, BIG CAS-OSLO Genome Research Cooperation, Disease Genomics and Individualized Medicine Laboratory, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1-7 Beichen West Road, Chaoyang District, Beijing 100101, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Li
authors.forename: Anja
authors.initials: A
authors.lastname: Nilsen
authors.forename: Yue
authors.initials: Y
authors.lastname: Shi
authors.forename: Markus
authors.initials: M
authors.lastname: Fusser
authors.forename: Yue-He
authors.initials: YH
authors.lastname: Ding
authors.forename: Ye
authors.initials: Y
authors.lastname: Fu
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Yamei
authors.initials: Y
authors.lastname: Niu
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Wu
authors.forename: Chun-Min
authors.initials: CM
authors.lastname: Huang
authors.forename: Maria
authors.initials: M
authors.lastname: Olofsson
authors.forename: Kang-Xuan
authors.initials: KX
authors.lastname: Jin
authors.forename: Ying
authors.initials: Y
authors.lastname: Lv
authors.forename: Xing-Zhi
authors.initials: XZ
authors.lastname: Xu
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
authors.forename: Jannie M
authors.initials: JM
authors.lastname: Rendtlew Danielsen
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.forename: Yun-Gui
authors.initials: YG
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism*; D000071501:AlkB Homolog 4, Lysine Demethylase; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D048749:Cytokinesis; D049308:Dioxygenases / Q000378:metabolism*; D020964:Embryo Loss / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D005816:Genetic Complementation Test; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding
chemical_list: D000199:Actins; D000205:Actomyosin; D049308:Dioxygenases; C557720:ALKBH4 protein, human; C585273:ALKBH4 protein, mouse; D000071501:AlkB Homolog 4, Lysine Demethylase; D002262:Carboxy-Lyases; D008239:Lysine