Heterocomplex Formation by Arp4 and β-Actin Involved in Integrity of the Brg1 Chromatin Remodeling Complex

• DOI: 10.1242/jcs.104349
• Publication Date: 2012-05-10T01:10:33Z
• Authors: Naoki Nishimoto; Masanori Watanabe; Shinya Watanabe; Nozomi Sugimoto; Takashi Yugawa; Tsuyoshi Ikura; Osamu Koiwai; Tohru Kiyono; Masatoshi Fujita
• Keywords: Models, Molecular; 0303 health sciences; Chromosomal Proteins, Non-Histone; Protein Conformation; Molecular Sequence Data; DNA Helicases; Nuclear Proteins; Chromatin Assembly and Disassembly; Transfection; Actins; Chromatin; DNA-Binding Proteins; Histones; 03 medical and health sciences; HEK293 Cells; Mutation; Humans; Amino Acid Sequence; HeLa Cells; Protein Binding; Transcription Factors

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. We have investigated the role of BAF53/human Arp4 in Brg1 chromatin remodeling complexes. Depletion of Arp4 by RNA interference impaired their integrity and accelerated degradation of Brg1, indicating a crucial role in 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 by which interactions with β-actin might be impaired. Some of them indeed caused reduced binding to β-actin. Interestingly, such mutant Arp4 proteins also showed reduced incorporation into Brg1 complexes and interactions with c-myc-associated complexes as well as Tip60 HAT complexes were also impaired. Based on these findings, we propose that β-actin-Arp4 complex formation may be a crucial feature in some chromatin-modifying enzyme complexes like the Brg1 complex.