Always on the Move: Overview on Chromatin Dynamics within Nuclear Processes

Abstract

Our genome is organized into chromatin, a dynamic and modular structure made of nucleosomes. Chromatin organization controls access to the DNA sequence, playing a fundamental role in cell identity and function. How nucleosomes enable these processes is an active area of study. In this review, we provide an overview of chromatin dynamics, its properties, mechanisms, and functions. We highlight the diverse ways by which chromatin dynamics is controlled during transcription, DNA replication, and repair. Recent technological developments have promoted discoveries in this area, to which we provide an outlook on future research directions.

Keywords: DNA sequence; chromatin dynamics; chromatin organization; nucleosome.

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The nucleosome. A. Crystal structure (left, PDB 1KX5) and cartoon representation (right) of the nucleosome. Front and side views are shown. The nucleosome dyad (Super Helical Location - SHL 0) is highlighted along with the other SHLs. The DNA entry and exit sites, as well as the histone N- and C-terminal tails, are also shown. A legend of the cartoon is included. B. Histone octamer surface electrostatic potential seen from the front and side view of the nucleosome structure (PDB 1KX5, ChimeraX-1.6.1 Coulombic electrostatic potential) shown with its electrostatic potential scale (red, white, and blue for negative, neutral, and positive potential respectively). Arrows point out the nucleosomal acidic patch on the nucleosome faces. C. Nucleosomes are assembled in a stepwise manner. First, a (H3–H4)₂ tetramer is deposited on DNA to form a tetrasome. Then, the two H2A and H2B dimers are incorporated to form a nucleosome. A hexasome is a nucleosome that misses one H2A–H2B dimer.

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Nucleosome and chromatin dynamics. A. Schematic representation of different nucleosome dynamics during breathing - unwrapping. Upon unwrapping of the DNA ends up to 15 bp, the histone octamer remains mostly unchanged, whereas unwrapping of up to 35 bp may cause destabilization of H2A–H2B dimers, inducing their loss when more than 35 bp of DNA is unwrap. B. Sliding indicates the movement of DNA along the octamer, to reposition the nucleosome on a different genomic position. C. Depiction of different subnucleosomal and noncanonical nucleosome structures: hexasome, hemisome, right-handed nucleosome, overlapping dinucleosome, and ditetrasome. Their key feature is mentioned. D. Nucleosome–nucleosome interactions control chromatin fiber organization. Nucleosomes can interact with each other in several ways, namely, side-to-side, face-to-side, and face-to-face. Zoom-in box: the face-to-face arrangement is mediated by the interaction between the H4 tail of one nucleosome and the acidic patch of the adjacent nucleosome. E. Linker histones can bind the nucleosome on the dyad position and interact with the linker DNA to control chromatin fiber organization. F-G. Simulated structures of chromatin fibers with 10N bp (30 bp, 11 nucleosomes) (F) or 10N+5 bp (25 bp, 12 nucleosomes) DNA linker length (G). The linker length affects the twist of the DNA linker between nucleosomes, resulting in distinct chromatin fiber structures. While the 10N bp array forms an organized fiber characterized by face-to-face interactions between nucleosomes (F), the 10N+5 bp displays a diverse organization with limited stable interactions between nucleosomes (G). The PDB used to generate the figures in panels F and G was a kind gift of Rosana Collepardo-Guevara and Jan Huertas Martin (Chen et al., 2024).

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Chromatin dynamics in different contexts. A. Chromatin dynamics during transcription. Chromatin remodelers control the positioning of nucleosomes at the Transcription Start Site (TSS), creating a Nucleosome Free Region (NFR) and positioning the +1 and −1 nucleosomes. The RNA polymerase complex (RNAPolII) is transcribed through the nucleosomes, with the support of the histone chaperones FACT and SPT6 (not depicted), and chromatin remodelers. The histones are rapidly transferred from the incoming DNA to the transcribed DNA, with minimal destabilization of the histones from DNA. They may result in H2A-H2B dimer loss, forming hexasomes behind RNAPolII, and they are only slightly shifted from their original position. High frequency of RNAPolII transcription limits the restoration of nucleosomes from hexasomes, resulting in a locally more accessible chromatin landscape. B. Chromatin dynamics during DNA replication. Parental chromatin is disassembled ahead of the replisome, and the parental histones are chaperoned by several replisome components to be recycled behind the replisome on newly replicated DNA strands. Separate pathways control the recycling of parental histones on the leading or lagging strand of replication forks (see the text). Concomitantly, newly synthesized (i.e., new) histones are deposited on the replicated strands to maintain nucleosome density. Following the assembly of nascent chromatin, the epigenome is restored by chromatin remodelers and epigenetic complexes (not depicted). C. Chromatin dynamics during DNA repair. When DNA damage occurs, the surrounding chromatin is marked as part of the DNA damage response pathway. For example, histone H2A.X phosphorylation occurred on Ser139 (gH2A.X). These marks recruit the DNA repair machineries to the site of DNA damage. This process alters the 3D organization of the surrounding chromatin. Generally, nucleosomes are temporarily destabilized leading to histone eviction, to allow DNA repair to occur. Next, nucleosomes are restored on the repaired DNA.