Snf2-family proteins: chromatin remodellers for any occasion

Abstract

Chromatin facilitates the housing of eukaryotic DNA within the nucleus and restricts access to the underlying sequences. Thus, the regulation of chromatin structure provides an excellent platform for regulating processes that require information stored within genomic DNA. Snf2 proteins are a family of helicase-like proteins that direct energy derived from ATP hydrolysis into the mechanical remodelling of chromatin structure. Here, we highlight some of the recent discoveries regarding this family of proteins and show Snf2 proteins have roles in many aspects of genetic metabolism. Recent developments include new insights into the mechanism for nucleosome spacing and histone dimer exchange; together with growing evidence for the involvement of Snf2 proteins in DNA repair.

Figure 1. The different outputs of Snf2-protein chromatin-remodelling machines

The different remodelling reactions (A being converted to B–E) are often catalysed by specific sub-families of Snf2 proteins. The reverse reactions (B–E being converted to A) are also possible and are often catalysed by a different Snf2 protein. This suggests that Snf2-domains in different Snf2-protein subfamilies have been tuned for different activities; either by variation in the sequence of the Snf2-domain itself or by additional protein domains and/or interaction partners. Nucleosomes are represented as coloured circles, the grey or blue lines represent DNA. Green segments in (E) indicate nucleosomes with altered histone content.

Figure 2. Different mechanisms for exchanging the histone content within nucleosomes

(A) SWR1 specifically removes canonical H2A (blue) from nucleosomes and replaces it with H2A.Z (green). (B) INO80 removes H2A.Z and replaces it with H2A (C) Some Snf2 proteins, such as yeast Fun30, exchange histones without apparent specificity. This may be used to dilute histone variants (white) within chromatin when there is an available excess of another histone, represented as canonical H2A in blue. (D) Unstable nucleosomes, such as those containing Cse4 (yellow), may be completely removed by SWI/SNF, allowing an alternative nucleosome to be assembled in its place. (E) ATRX recognises G4 DNA (magenta) and may incorporate H3.3 nucleosomes (purple and blue) at these sites via an interaction with DAXX.

Figure 3. Structural basis for allosteric regulation of the Snf2-domain from Chd1

In Chd1 (PDB ID: 3MWY) the two RecA lobes (blue and orange) of the Snf2-domain are splayed apart and stabilised in an open conformation by the chromodomains (green). This conformation is incompetent for ATP hydrolysis as RecA lobe 2 (orange) is not in contact with the ATP molecule (red). Structures of the related zebrafish Rad54 Snf2-domain (PDB ID: 1Z3I) and Vasa SF2 RNA helicase (PDB ID: 2DB3) in a closed ATPase competent conformation are shown for comparison. In these structures RecA lobe 1 and 2 are in close proximity and the ATP-binding pocket is buried between the two lobes (a red shadow can be seen through the surface). The chromodomains obscure a putative nucleic acid binding surface on lobe 2, the equivalent surface in Vasa, which is occupied by RNA (yellow), is circled. Binding of the chromodomains to a surface on the nucleosome is thought to release the Snf2-domain into an active state.