Recent Advances in Investigating Functional Dynamics of Chromatin

Abstract

Dynamics spanning the picosecond-minute time domain and the atomic-subcellular spatial window have been observed for chromatin in vitro and in vivo. The condensed organization of chromatin in eukaryotic cells prevents regulatory factors from accessing genomic DNA, which requires dynamic stabilization and destabilization of structure to initiate downstream DNA activities. Those processes are achieved through altering conformational and dynamic properties of nucleosomes and nucleosome–protein complexes, of which delineating the atomistic pictures is essential to understand the mechanisms of chromatin regulation. In this review, we summarize recent progress in determining chromatin dynamics and their modulations by a number of factors including post-translational modifications (PTMs), incorporation of histone variants, and binding of effector proteins. We focus on experimental observations obtained using high-resolution techniques, primarily including nuclear magnetic resonance (NMR) spectroscopy, Förster (or fluorescence) resonance energy transfer (FRET) microscopy, and molecular dynamics (MD) simulations, and discuss the elucidated dynamics in the context of functional response and relevance.

Exploring Therapeutic Potential of Nutraceutical Compounds from Propolis on MAPK1 Protein Using Bioinformatics Approaches as Anti-Coronavirus Disease 2019 (COVID-19)

“…The findings of combinations of proteins associated with Propolis and COVID-19 were then filtered using the parameter P-value <0.05 to quantify statistical differences and target potential [42]- [44]. The Gene Ontology of Biological Process and KEGG target data were shown using the Bioinformatics website platform (http://www.bioinformatics.com.cn) [45]- [48] and GraphPad Prism 9.0.0.…”

The SMC5/6 complex: folding chromosomes back into shape when genomes take a break

“…The organization of chromatin in space is one of the key determinants of the functional state of genes and genomes. Several decades of research has revealed that open or accessible chromatin generally promotes DNA transactions while densely folded chromatin significantly limits enzyme mobility and access to DNA substrates ( 1 , 2 ). Eukaryotic organisms take advantage of the ability to finely tune the organization of chromatin in space to enhance the efficiency, fidelity, and regulation of vital cellular processes such as gene transcription, DNA repair and genome segregation.…”

“…Changes in chromatin state is a complex affair typically requiring multi-step processes that involve nucleosomes, post-translational modifications (PTMs) of histones, as well as chromatin remodeling enzymes ( 1 , 2 ). This paradigm represents the prevalent view of how chromatin organization is regulated in interphase cells.…”

Histone H3 core domain in chromatin with different DNA linker lengths studied by 1H-Detected solid-state NMR spectroscopy

“…While significant progress has been made in atomic-resolution structure determination for nucleosomes, nucleosome arrays and their complexes with chromatin binding proteins by X-ray crystallography and, more recently, cryo-electron microscopy ( Zhou et al, 2019 ; Bai and Zhou, 2021 ; Takizawa and Kurumizaka, 2022 ), as well as characterization of conformational dynamics of histone tail and core domains in mononucleosomes by solution-state nuclear magnetic resonance (NMR) spectroscopy ( Musselman and Kutateladze, 2022 ), studies of histone protein structure, conformational dynamics and interactions in condensed nucleosomes and nucleosome arrays representative of chromatin at physiological concentrations come with considerable challenges that can uniquely be addressed by using magic angle spinning solid-state NMR techniques ( van Emmerik and van Ingen, 2019 ; Ackermann and Debelouchina, 2021 ; Shi et al, 2022 ). Indeed, these solid-state NMR studies have revealed that histone N-terminal tails retain considerable conformational flexibility even in the highly condensed chromatin environment ( Gao et al, 2013 ; Shi et al, 2018 ; Xiang et al, 2018 ; Shi et al, 2020a ; Zandian et al, 2021 ), which likely plays a significant role in recruitment of chromatin regulatory proteins, and enabled histone core dynamics ( Shi et al, 2020b ), base pairing in nucleosomal DNA ( Conroy et al, 2022 ), histone protein interactions with nucleosomal DNA ( Elathram et al, 2022 ) and with nucleosome binding peptides and proteins ( Xiang et al, 2018 ; le Paige et al, 2021 ), as well as the impact of PTMs on histone tail conformation and flexibility ( Shoaib et al, 2021 ) to be probed with atomic-resolution detail.…”