Chromatin remodeling: insights and intrigue from single-molecule studies

Abstract

Chromatin remodelers are ATP-hydrolyzing machines specialized to restructure, mobilize or eject nucleosomes, allowing regulated exposure of DNA in chromatin. Recently, remodelers have been analyzed using single-molecule techniques in real time, revealing them to be complex DNA-pumping machines. The results both support and challenge aspects of current models of remodeling, supporting the idea that the remodeler translocates or pumps DNA loops into and around the nucleosome, while also challenging earlier concepts about loop formation, the character of the loop and how it propagates. Several complex behaviors were observed, such as reverse translocation and long translocation bursts of the remodeler, without appreciable DNA twist. This review presents and discusses revised models for nucleosome sliding and ejection that integrate this new information with the earlier biochemical studies.Many processes involving chromosomes are guided by DNA-binding proteins, and the access of these proteins to DNA is regulated by chromatin. Nucleosomes, the primary repeating unit of chromatin, package DNA by wrapping 147 base pairs (bp) around an octamer of histone proteins in ∼1.7 helical turns 1-3 . This packaging provides topological order but occludes one face of the DNA, which slows or prevents the recognition of DNA sequences by DNA-binding proteins. To maintain topological order, and also to allow rapid and regulated access to the DNA, cells have evolved a set of chromatin-remodeling machines that alter nucleosome position, presence and structure.Remodelers can be separated into several families on the basis of their composition and activities: SWI/SNF, ISWI, NURD/Mi-2/CHD and the 'split ATPases' INO80 and SWR1 (which bear an insertion within their ATPase domains). Rad54 may represent an additional family, as it perturbs chromatin in vitro, but it apparently lacks specific nucleosome-interacting domains 4,5 . The participation of remodelers in various chromosomal processes has been the subject of many reviews 6-9 . The present work focuses solely on remodeler mechanisms, and primarily on the function of their conserved catalytic subunit, a superfamily 2 (SF2) ATPdependent DNA translocase. Recently, single-molecule approaches have been used to examine several remodelers, providing many new insights into their behavior. Here I discuss these recent studies, compare them with previous biochemical studies and suggest refinements to existing models to account for some of the observations. Remodelers slide, eject and restructure nucleosomesRemodelers can affect nucleosomes in at least four ways ( Fig. 1): (i) sliding, or moving the histone octamer to a new position, which exposes DNA 10-12 ; (ii) ejection, or completely displacing the octamer to expose DNA [13][14][15][16] ; (iii) removal of H2A-H2B dimers, leaving only the central H3-H4 tetramer, which exposes DNA and destabilizes the nucleosome 17,18 ; and (iv) dimer replacement-for example, exchanging the resident H2A-H2B dimers for dimers NIH Public Access

Nucleosome Remodeling and Epigenetics

“…This bulge would then be propagated by the transIocase activity over the histone octamer surface. This DNA translocation of the ATPase domain on the nucleosome causes a twisting of the DNA, which induces a local superhelical strain into the DNA (Lia et al 2006;Cairns 2007). Nucleosome remodeling thus presumably involves a combination of translational and rotational displacement of DNA.…”

Green Evolution and Dynamic Adaptations Revealed by Genomes of the Marine Picoeukaryotes Micromonas

“…histone chaperones such as NAP1 homologs (46), chromatin assembly factors CAC1, CAC2 and CAC3 (47), the HIR class of chaperones (48), FACT complex subunits SSRP1/POB3 (49), ASF1 (50), and most of the nucleosome remodeling proteins that disassemble and move nucleosomes during transcription and DNA replication (table S6). The latter group includes the SWI/SNF superfamily of ATPdependent nucleosome remodelers that influence chromatin structure through the disruption of histone-DNA interactions to slide and reposition nucleosomes (51).…”

Basic concepts of epigenetics

“…The unstable dimer is collapsible, highly acetylated and enables chromatin expansion and nucleosome ejection at areas of unmethylated DNA targeted for active expression. 89 Unstable histone variants such as H2A.Z most often coincide with transcription start sites 90,91 and are highly concentrated in euchromatin marked with acetylated H3K9, H3K18, H3K27 and H4 tails circumscribing open 5' promoter regions of genes. 92,93 While methylation of histone tails is primarily associated with silencing, triple methylation at H2AR at serine residues within the H3 tail by enzymes such as PRMT5 are also associated with H2A.Z core exchange, unit collapse, nucleosomal ejection and active gene expression.…”