Chromatin Remodelers : Case Study

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In addition to histone modifications and DNA methylation, chromatin remodeling ATPases and their associated complexes also participate in transcriptional regulation by controlling the positioning, occupancy and composition of nucleosomes (Han, Wu, Cui, & Wagner, 2015; Sudarsanam & Winston, 2000). Chromatin remodelers are large, multi-protein complexes that alter the interaction between DNA and the histone octamer non-covalently (Clapier & Cairns, 2009; Hargreaves & Crabtree, 2011) and assist the transcriptional responses at the expense of ATP (Vignali, Hassan, Neely, & Workman, 2000). In addition to the central ATP hydrolase subunit, each remodeler complex contains unique, specialized proteins that aid in the complex’s activity…show more content…
Histone chaperones facilitate incorporation of histones on DNA by neutralizing their positive charges, and thus play key roles in regulating nucleosome assembly (Philpott, Krude, & Laskey, 2000). Nucleosomes are assembled via a stepwise process. First, the H3–H4 tetramer is deposited on DNA, followed by the addition of two H2A–H2B dimers (S. Smith & Stillman, 1991). This process is reversible to allow disassembly of nucleosomes (Figure 6B). Each of the canonical histones is encoded by multiple genes and most of these genes are organized into clusters throughout the genome to ensure that the expression of canonical histones during S-phase generates large and equal amounts of all four nucleosome core histone proteins (Albig, Kioschis, Poustka, Meergans, & Doenecke, 1997). Figure 6. (A) Structure of the nucleosome core particle with (H3/H4)2 at the center of the DNA wrap and (H2A/H2B)2 docked at the edges, near the DNA entry and exit locations. (B) Nucleosomes control access to certain binding sites. Transient DNA unwrapping exposes the binding sites. As nucleosomes unwrap, H2A/H2B dimers can be lost, exposing more DNA, and when the nucleosome is completely unwrapped, (H3/H4)2 is lost, and DNA is completely exposed. This image was taken from a previous publication (Weber & Henikoff, 2014).

One form of altering chromatin structure is through the deposition of histone variants, related protein isoforms encoded by non-allelic
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