Sophisticated Conversations between Chromatin and Chromatin Remodelers, and Dissonances in Cancer

Abstract

The establishment and maintenance of genome packaging into chromatin contribute to define specific cellular identity and function. Dynamic regulation of chromatin organization and nucleosome positioning are critical to all DNA transactions—in particular, the regulation of gene expression—and involve the cooperative action of sequence-specific DNA-binding factors, histone modifying enzymes, and remodelers. Remodelers are molecular machines that generate various chromatin landscapes, adjust nucleosome positioning, and alter DNA accessibility by using ATP binding and hydrolysis to perform DNA translocation, which is highly regulated through sophisticated structural and functional conversations with nucleosomes. In this review, I first present the functional and structural diversity of remodelers, while emphasizing the basic mechanism of DNA translocation, the common regulatory aspects, and the hand-in-hand progressive increase in complexity of the regulatory conversations between remodelers and nucleosomes that accompanies the increase in challenges of remodeling processes. Next, I examine how, through nucleosome positioning, remodelers guide the regulation of gene expression. Finally, I explore various aspects of how alterations/mutations in remodelers introduce dissonance into the conversations between remodelers and nucleosomes, modify chromatin organization, and contribute to oncogenesis.

Differential Histone-DNA Interactions Dictate Nucleosome Recognition of the Pioneer Transcription Factor Sox

“…Relatedly, it was recently shown that SHL2 can harbor nonspecific protein binding, as revealed by the TATA-box-binding-protein:SHL2 complex (65). At the SHL2 H3 α3and H4 α2-helices form very few protein contacts, providing an extra flexibility to this region (66)(67)(68)(69). All in all, it is clear that weak histone-DNA interactions at SHL2 makes SHL2 a good recognition site for Sox.…”

Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer, Part 1: Technical Considerations

“…Chromatin dynamics rely mainly on posttranslational modifications (PTMs), nucleosome positioning and spatial genome organization; these modifications are involved in complex crosstalk with DNA methylation [ 56 ]. Currently, there is no clinical proof that such epigenetic modifications can directly lead to HRD in the context of OC [ 57 ]. However, as chromatin can act as a gene silencer and a barrier to efficient DNA repair, it appears plausible that chromatin remodeling could partly explain (or at least participate in) HRD in OC [ 58 ].…”

Optical Imaging of Epigenetic Modifications in Cancer: A Systematic Review

“…In eukaryotic cells, chromatin refers to a linear composite structure comprising DNA, histones, nonhistone proteins, and RNA (Kornberg and Thomas 1974). Chromatin modifiers regulate the chromatin structure by influencing the assembly, disassembly, and rearrangement of the nucleosomes on the chromatin, thereby improving the localization of the transcription factors and other transcription-related elements in the chromatin DNA (Clapier 2021;Reyes et al 2021). The chromatin structure changes dynamically in cells, and was distinct at different epigenomic states (Xu et al 2018) (Fig.…”