ATP-Dependent Nucleosome Remodeling

Abstract

It has been a long-standing challenge to decipher the principles that enable cells to both organize their genomes into compact chromatin and ensure that the genetic information remains accessible to regulatory factors and enzymes within the confines of the nucleus. The discovery of nucleosome remodeling activities that utilize the energy of ATP to render nucleosomal DNA accessible has been a great leap forward. In vitro, these enzymes weaken the tight wrapping of DNA around the histone octamers, thereby facilitating the sliding of histone octamers to neighboring DNA segments, their displacement to unlinked DNA, and the accumulation of patches of accessible DNA on the surface of nucleosomes. It is presumed that the collective action of these enzymes endows chromatin with dynamic properties that govern all nuclear functions dealing with chromatin as a substrate. The diverse set of ATPases that qualify as the molecular motors of the nucleosome remodeling process have a common history and are part of a superfamily. The physiological context of their remodeling action builds on the association with a wide range of other proteins to form distinct complexes for nucleosome remodeling. This review summarizes the recent progress in our understanding of the mechanisms underlying the nucleosome remodeling reaction, the targeting of remodeling machines to selected sites in chromatin, and their integration into complex regulatory schemes.

Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60

“…These remodeling factors do not affect the biochemical properties of nucleosomes. Instead, they use the energy from ATP to slide nucleosomes along a particular DNA sequence, alter DNA-histone interactions, ease histone exchange or even enable complete removal of histones at a specific location (Becker and Horz, 2002). As chromatin remodeling factors need the energy from ATP-hydrolysis, they all have an ATPase subunit and therefore can be grouped according to the sequence of this subunit.…”

Structural evidence for Nap1‐dependent H2A–H2B deposition and nucleosome assembly

“…Spatial and temporal regulation of specific chromatin loci by dynamic assembly of nucleosomes is essential for the control of DNA‐templated processes such as replication, DNA damage repair, and gene regulation (Venkatesh & Workman, 2015). The nucleosome serves as a general transcriptional repressor, and promoter nucleosome removal is an early step in gene activation (Becker & Horz, 2002; Bryant et al , 2008). Thus, the ordered disassembly and reassembly of nucleosomes is an important paradigm in gene regulation.…”

Mechanisms of ATP dependent chromatin remodeling

“…The first kind involves covalent modifications of the histone N-terminal tails and occurs without the hydrolysis of ATP [2]. The second mode requires the hydrolysis of ATP and involves the movement of histone octamers relative to DNA in order to make the DNA accessible [3]. Even though these mechanisms are distinct, they are functionally interconnected inside the cell.…”