Journal of Molecular Biology
PerspectiveLocal Chromatin Motion and Transcription
Graphical abstract
Introduction
All essential DNA-templated processes (e.g., RNA transcription, DNA replication, repair/recombination) in eukaryotic cells occur in the context of chromatin [[1], [2], [3], [4]]. The fundamental unit of chromatin is the nucleosome, comprised of genomic DNA wrapped around an octamer of core histone proteins that regulate the access of DNA-templated processes to genetic information [5]. For higher order chromatin folding, based on initial in-vitro observations, the nucleosome fiber was predicted to helically fold upon itself to form a highly ordered “30-nm fiber” [6,7] and further large regular fibers. However, further studies found the regular 30-nm fibers only under a few rare conditions, for instance, under low salt conditions [8], or very partially and transiently [9]. Instead, chromatin was mainly found to consist of more irregular and variable nucleosome fibers [[9], [10], [11], [12], [13], [14], [15], [16], [17]]. Chromatin exists in a fluid-like state in the living cell. In this perspective, we define the fluid-like chromatin state as one with diffusive movement, as opposed to vibration around a fixed position found in amorphous solids [18,19]. Note that this state is contrasted with the static state that has long been proposed based on the regular 30-nm fibers [20,21]. The biophysical properties of this dynamic chromatin also fit well with parameters such as bendability obtained from chromatin conformation capture (3C) and related experiments [[22], [23], [24]]. Taken together, extensive advances in the past 10 years have highlighted the dynamic organization of chromatin in the nucleus and its significance in regulating genomic processes. In this perspective, we will discuss the dynamic aspect of chromatin, especially its interplay with transcription.
Section snippets
Local Chromatin Motion
Dynamic movements of chromatin in live-cell imaging studies have long been revealed using LacO/LacI-GFP [[25], [26], [27], [28], [29]] and a related system [30,31], CRISPR/dCas9-based strategies [[32], [33], [34]], and single nucleosome imaging [35,36]. Genome-wide chromatin dynamics in a whole nucleus were also investigated using fluorescently labeled chromatin [[37], [38], [39]]. This dynamic property ensures a degree of DNA accessibility, even in compacted chromatin [35,40], which was also
Transcription as a Regulator of Chromatin Motion
Recently it was shown that active RNA polymerase II (RNAPII) has a constraining role for chromatin motion in the cell [57]. RNAPII is a multisubunit complex that is responsible for the transcription of all protein-coding mRNAs and many additional noncoding RNAs [58,59]. That RNAPII normally constricts chromatin movement was a surprising finding because it was previously assumed that transcription would open up chromatin structure and increase local chromatin motion. However, it was demonstrated
Perspectives
Over the past 10 years, there has been a growing appreciation for the highly variable and dynamic nature of chromatin organization and how these properties can contribute to regulating cellular processes including RNA transcription, DNA replication, and repair/recombination. Recently it was shown that globular structures, which chromatin can form with Mg2+ in vitro [8], have liquid droplet property [79]. This progress raises a concern that detailed structural determination of chromatin might
Acknowledgments
We are grateful to the collaborators in the Nagashima et al. (2019) for their contribution, Ms. Sachiko Tamura for the Figure preparation. We thank Dr. M. Sasai and Dr. S. Ide for critical reading of this manuscript, and Dr. Bystricky and Maeshima lab members for helpful discussions, and the anonymous reviews for their valuable comments to improve this manuscript. We apologize that we could not mention many important works and related papers on chromatin dynamics due to space limitations. This
References (81)
- et al.
Structure, function and dynamics of nuclear subcompartments
Curr. Opin. Cell Biol.
(2012) - et al.
Structural and functional diversity of topologically associating domains
FEBS Lett.
(2015) - et al.
Chromatin fibers are formed by heterogeneous groups of nucleosomes in vivo
Cell
(2015) - et al.
Sub-nucleosomal genome structure reveals distinct nucleosome folding motifs
Cell
(2019) - et al.
Chromatin hydrodynamics
Biophys. J.
(2014) - et al.
Dynamic chromatin organization without the 30-nm fiber
Curr. Opin. Cell Biol.
(2019) Mapping in vivo chromatin interactions in yeast suggests an extended chromatin fiber with regional variation in compaction
J. Biol. Chem.
(2008)- et al.
Mapping nucleosome resolution chromosome folding in yeast by Micro-C
Cell
(2015) - et al.
Chromatin motion is constrained by association with nuclear compartments in human cells
Curr. Biol.
(2002) - et al.
Interphase chromosomes undergo constrained diffusional motion in living cells
Curr. Biol.
(1997)
Real-time imaging of a single gene reveals transcription-initiated local confinement
Biophys. J.
3D trajectories adopted by coding and regulatory DNA elements: first-passage times for genomic interactions
Cell
Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system
Cell
Local nucleosome dynamics facilitate chromatin accessibility in living mammalian cells
Cell Rep.
Dynamic organization of chromatin domains revealed by super-resolution live-cell imaging
Mol. Cell
Chromatin dynamics in interphase cells revealed by tracking in a two-photon excitation microscope
Biophys. J.
Visualization of chromatin decompaction and break site extrusion as predicted by statistical polymer modeling of single-locus trajectories
Cell Rep.
Establishing and dissolving cohesion during the vertebrate cell cycle
Curr. Opin. Cell Biol.
Cohesion and cohesin-dependent chromatin organization
Curr. Opin. Cell Biol.
Lamina-associated domains: links with chromosome architecture, heterochromatin, and gene repression
Cell
Structural basis of heterochromatin formation by human HP1
Mol. Cell
The energetics and physiological impact of cohesin extrusion
Cell
Why the activity of a gene depends on its neighbors
Trends Genet.
The cell in absence of aggregation artifacts
Micron
Imaging RNA Polymerase II transcription sites in living cells
Curr. Opin. Genet. Dev.
Transcription Factories: Genetic Programming in Three Dimensions
Curr. Opin. Genet. Dev.
The spatial organization of the human genome
Annu. Rev. Genomics Hum. Genet.
Nuclear compartmentalization, dynamics, and function of regulatory DNA sequences
Genes Chromosomes Cancer
Crystal structure of the nucleosome core particle at 2.8 A resolution
Nature
Solenoidal model for superstructure in chromatin
Proc. Natl. Acad. Sci. U. S. A.
Cryo-EM study of the chromatin fiber reveals a double helix twisted by tetranucleosomal units
Science (New York, NY)
Nucleosomal arrays self-assemble into supramolecular globular structures lacking 30-nm fibers
EMBO J.
Variable chromatin structure revealed by in situ spatially correlated DNA cleavage mapping
Nature
Analysis of cryo-electron microscopy images does not support the existence of 30-nm chromatin fibers in mitotic chromosomes in situ
Proc. Natl. Acad. Sci. U. S. A.
Open and closed domains in the mouse genome are configured as 10-nm chromatin fibres
EMBO Rep.
Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure
Embo J
Budding yeast chromatin is dispersed in a crowded nucleoplasm in vivo
Mol. Biol. Cell
ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells
Science (New York, NY)
Cryo-ET reveals the macromolecular reorganization of S. pombe mitotic chromosomes in vivo
Proc. Natl. Acad. Sci. U. S. A.
Organization of fast and slow chromatin revealed by single-nucleosome dynamics
Proc. Natl. Acad. Sci. U. S. A.
Cited by (0)
- †
These authors contributed equally to this manuscript.