Journal of Molecular Biology
Volume 432, Issue 3, 7 February 2020, Pages 694-700
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Perspective
Local Chromatin Motion and Transcription

https://doi.org/10.1016/j.jmb.2019.10.018Get rights and content

Highlights

  • Chromatin is predominantly folded irregularly inside the nucleus in a fluidlike state.

  • Local chromatin movements, driven principally by thermal fluctuation, are constrained by multiple different proteins.

  • Active RNA polymerase II globally constrains chromatin motion, forming loose genome chromatin networks.

Abstract

Eukaryotic chromatin is a complex of nucleic acids and proteins that is central to interpreting the information coded in the genome. Chromatin is rather irregularly folded inside the nucleus in a fluid-like state that exhibits dynamic local movement. The highly dynamic nature of chromatin has become increasingly appreciated, particularly in DNA-templated processes including transcription, because this dynamic property ensures a degree of DNA accessibility, even in compacted chromatin. Many proteins globally constrain local chromatin movements, which seem to be driven essentially by thermal fluctuation in living cells. For instance, loss of the cohesin complex, which can capture chromatin fibers, leads to an increase in chromatin motion. Another constraining factor of chromatin motion is the transcription machinery. Although the previously held view is that transcription requires open and highly dynamic chromatin, a number of studies are now pointing to a more nuanced role of transcription in constraining chromatin movement: dynamic clustering of active RNA polymerase II and other transcription factors can serve as a hub that transiently bridges active DNA regions to be transcribed, thereby loosely networking chromatin and constraining chromatin motion. In contrast, outside heterochromatin, the transcriptionally less active regions might be less constrained, more dynamic and accessible, implying a high competency state for rapid and efficient recruitment of protein factors. This new view on the interplay of local chromatin motion and transcription reflects traditional models of the transcription factories and, more recently, liquid droplets of transcription factors, providing new insight into chromatin function.

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

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