The nuclear actin-related proteins, Arp7 and Arp9: connecting ARP hetertodimerization to the regulation of chromatin remodling.

Actin-related proteins (ARPs) belong to the actin superfamily of proteins with diverse functions in both the cytoplasm and the nucleus. ARPs share limited sequence similarity to actin, but have conserved the 'actin-fold' utilized by actin for ATP binding and hydrolysis. Intriguingly, nuclear ARPs and actin are members of two types of chromatin modifying complexes; chromatin remodeling complexes that mobilize nucleosomes in an ATP-dependent manner and histone acetyltransferase (HAT) complexes that posttranslationally modify nucleosomes by covalently linking an acetyl group to lysine residues on histones. Although ARPs/actin are not subunits of all types of remodelers and HATs, they are found in particular families, including the SWI/SNF family of remodelers and the MYST family of HATS. The central question is: how are ARPs utilized in the regulation of chromatin structure? Heterodimerization is an essential property of cytoplasmic ARPs in the cytoskeleton. Our work reveals Arp7 and Arp9 as obligate heterodimers both physically and functionally, as dimerization is a prerequisite for their assembly into the related RSC and SWI/SNF remodeling complexes in S. cerevisiae . Additionally, we found that Arp7 and Arp9 interact with two regulators of chromatin structure including Nhp6 (n[barbelow]on-h[barbelow]istone p[barbelow]rotein 6[barbelow]), an HMG-box architectural factor, and Sth1, the catalytic subunit (DNA translocase) of RSC. arp7/arp9 conditional alleles were partially suppressed by overexpression of NHP6 suggesting a role for ARPs in the regulation of promoter architecture. Arp7/Arp9-mediated regulation of chromatin structure may be through their association with RSC, as mutations in either the ATPase domain or the HSA (helicase/SANT-associated) domain of Sth1 resulted in the partial bypass of Arp7/Arp9 function. Taken together, our data suggest that Arp7/Arp9 dimers cooperate with particular domains of Sth1 in the regulation of the RSC complex.