The dynamic nature of chromatin and its epigenetic information content are regulated by numerous chromatin modifying enzymes. Among those are ATP dependent remodelers, which slide or evict nucleosomes, or exchange histone variants, as well as enzymes that add, alter or remove posttranslational modifications on histones and DNA.1
Several of these chromatin remodeling and modifying complexes including INO80, SWR1, RSC, NuA4 and SWI/SNF contain actin and actin-related proteins (Arps) as subunits.2–6
Arps and actin are often integrated into these complexes as pairs like for example the Arp4—actin pair and bind to a domain present in the Swi2/Snf2 ATPase subunit of the remodelers, the helicase—SANT associated (HSA) domain.7
Several nuclear Arps have been shown to interact with histones, suggesting a function in targeting their remodelers to the chromatin substrate.8–11
The mammalian INO80 complex for example is targeted to DNA damage sites in an Arp8 dependent manner.12
Nevertheless, additional functions of Arps within the chromatin modifying complexes and the functional role of actin and the actin-Arp interactions remain elusive. depicts a model of the INO80 chromatin remodeling complex that contains an Arp4-Arp8-actin subcomplex.
Figure 1 (A) Potential architecture of the INO80 complex. The 15 principal subunits are depicted with the INO80 protein acting as a scaffold to integrate them into the complex. Different domains within the INO80 protein are labeled. The N-terminal HSA domain acts (more ...)
The functional understanding of nuclear Arps, which appear to be specific for chromatin modifying complexes, is further hampered by a general lack of understanding of the properties of actin in the nucleus. In fact, roles of nuclear actin and its polymerization state are still rather controversial, as phalloidin stainable actin filaments are not observed in the nucleus.13
Nevertheless, nuclear actin has been implicated to function in long-range chromatin movement and is required for proper transcriptional activity of all three RNA polymerases.14,15
In particular, the inhibition of polymeric actin by latrunculin in vivo inhibits RNA transcription.16
Likewise, inhibition of RNA polymerase I mediated by an antibody directed against actin can only be overcome by providing polymerization competent actin but not by actin mutants that do not support filament formation.17
Several studies have also shown that the movement of nuclear loci exhibits the characteristics of an active transport process and is dependent on polymeric nuclear actin.14,18,19
In short, some polymeric forms of actin seem to play important roles in nuclear processes and there is presumably a need for regulation of nuclear actin polymerization.