Multiple modes of regulation of the human Ino80 SNF2 ATPase by subunits of the INO80 chromatin-remodeling complex

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 51; pp. 20497 - 20502
• Main Authors: Lu Chen, Conaway, Ronald C., Conaway, Joan W.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.12.2013; NATIONAL ACADEMY OF SCIENCES; National Acad Sciences
• Subjects: Adenosine triphosphatase; Adenosine triphosphatases; adenosinetriphosphatase; Angiopoietin-like Proteins; Angiopoietins - genetics; Angiopoietins - metabolism; Biological Sciences; catalytic activity; Cell lines; Chromatin; Chromatin Assembly and Disassembly - physiology; DNA; DNA Helicases - genetics; DNA Helicases - metabolism; Health savings accounts; HEK293 Cells; HeLa Cells; histidine; Humans; inositols; Microbiology; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; Nucleosomes; Nucleosomes - enzymology; Nucleosomes - genetics; Proteins; Renovations; Small interfering RNA; Substrates; Yeasts; zinc finger motif; Zinc Fingers; INO80 complex; enzyme activity
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1317092110

SNF2 family ATPases are ATP-dependent motors that often function in multisubunit complexes to regulate chromatin structure. Although the central role of SNF2 ATPases in chromatin biology is well established, mechanisms by which their catalytic activities are regulated by additional subunits of chromatin-remodeling complexes are less well understood. Here we present evidence that the human Inositol auxotrophy 80 (Ino80) SNF2 ATPase is subject to regulation at multiple levels in the INO80 chromatin-remodeling complex. The zinc finger histidine triad domain-containing protein Ies2 (Ino Eighty Subunit 2) functions as a potent activator of the intrinsic catalytic activity of the Ino80 ATPase, whereas the YL-1 family Ies6 (Ino Eighty Subunit 6) and actin-related Arp5 proteins function together to promote binding of the Ino80 ATPase to nucleosomes. These findings support the idea that both substrate recognition and the intrinsic catalytic activities of SNF2 ATPases have evolved as important sites for their regulation.