title: Heterocomplex formation by Arp4 and β-actin is involved in the integrity of the Brg1 chromatin remodeling complex.
abstract: Although nuclear actin and Arps (actin-related proteins) are often identified as components of multi-protein chromatin-modifying enzyme complexes, such as chromatin remodeling and histone acetyltransferase (HAT) complexes, their molecular functions still remain largely elusive. Here, we investigated the role of human Arp4 (BAF53, also known as actin-like protein 6A) in Brg1-containing chromatin remodeling complexes. Depletion of Arp4 by RNA interference impaired the integrity of these complexes and accelerated the degradation of Brg1, indicating a crucial role in their maintenance, at least in certain human cell lines. We further found that Arp4 can form a heterocomplex with β-actin. Based on structural similarities between conventional actin and Arp4, and the assumption that actin-Arp4 binding might mimic actin-actin binding, we introduced a series of mutations in Arp4 that might be expected to impair its interaction with β-actin. Some of them indeed caused reduced binding to β-actin. Interestingly, such mutant Arp4 proteins also showed reduced incorporation into Brg1 complexes, and their interaction with Myc-associated complexes as well as Tip60 HAT complexes were also impaired. Based on these findings, we propose that β-actin-Arp4 complex formation might be a crucial feature in some chromatin-modifying enzyme complexes, such as the Brg1 complex.
authors.affiliation: Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuohku, Tokyo 104-0045,  Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nishimoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Watanabe
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.forename: Nozomi
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Yugawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
authors.forename: Osamu
authors.initials: O
authors.lastname: Koiwai
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Fujita
mesh_terms: D000199:Actins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C116160:ACTL6A protein, human; D000199:Actins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases