Primary Role of the Nucleosome

Kornberg, Roger D.; Lorch, Yahli

doi:10.1016/j.molcel.2020.07.020

Cited by 130 publications

(77 citation statements)

References 74 publications

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“…Key cellular processes, such as replication, recombination and transcription depend in part on the positioning and the dynamics of the nucleosomes ( 2 , 3 ). Because the primary function of nucleosomes is the regulation of transcription ( 4 ), it is important to understand the forces that govern the stability of the nucleosome, and the mechanism by which DNA unwraps and rewraps.…”

Section: Introductionmentioning

confidence: 99%

Asymmetry in histone rotation in forced unwrapping and force quench rewrapping in a nucleosome

Reddy

Thirumalai

2021

Nucleic Acids Research

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Single molecule pulling experiments have shown that DNA in the nucleosomes unwraps in two stages from the histone protein core (HPC). The first stage, attributed to the rupture of the outer DNA turn, occurs between 3 and 5 pNs, and is reversible. The inner DNA turn ruptures irreversibly at forces between 9 and 15 pNs (or higher) in the second stage. Molecular simulations using the Self-Organized Polymer model capture the experimental findings. The unwrapping of the outer DNA turn is independent of the pulling direction. The rupture of the DNA inner turn depends on the pulling direction and involves overcoming substantial energetic (most likely electrostatic in origin) and kinetic barriers. They arise because the mechanical force has to generate sufficient torque to rotate the HPC by 180°. On the other hand, during the rewrapping process, HPC rotation is stochastic, with force playing no role. The assembly of the outer DNA wrap upon force quench nearly coincides with the unwrapping process, confirming the reversibility of the outer turn rupture. The asymmetry in HPC rotation during unwrapping and rewrapping explains the observed hysteresis in the stretch-release cycles in experiments. We propose experiments to test the prediction that HPC rotation produces kinetic barriers in the unwrapping process.

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Section: Introductionmentioning

confidence: 99%

Asymmetry in histone rotation in forced unwrapping and force quench rewrapping in a nucleosome

Reddy

Thirumalai

2021

Nucleic Acids Research

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“…Nucleosomes pose a significant barrier to transcription (Bondarenko et al, 2006;Chen et al, 2019;Izban and Luse, 1992;Kireeva et al, 2002), but highly transcribed genes show reduced nucleosomal occupancy and decompaction (Chambeyron and Bickmore, 2004;Dultz et al, 2018;Wittner et al, 2011). It has been proposed that nucleosomes evolved to specifically regulate transcription (Kornberg and Lorch, 2020). Supporting this idea, surfaces on RNA polymerase II that are only conserved among eukaryotes directly contact the nucleosome (Cramer et al, 2001;Farnung et al, 2018;Kujirai et al, 2018;Figure 3A).…”

Section: Naps and Chromatinmentioning

confidence: 99%

Understanding transcription across scales: From base pairs to chromosomes

Vos

2021

Molecular Cell

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“…Eukaryotic chromatin is organized by nucleosomes, which package and regulate access to DNA and whose primary role may be to globally repress transcription (Kornberg and Lorch, 2020). Nucleosomes are formed from an octameric core particle of two molecules each of the histones H2A, H2B, H3 and H4, which wraps 147 bp of DNA (Luger et al, 1997) (see poster).…”

Section: Introductionmentioning

confidence: 99%

Histone variants at a glance

Talbert

Henikoff

2021

Journal of Cell Science

124

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Eukaryotic nucleosomes organize chromatin by wrapping 147 bp of DNA around a histone core particle comprising two molecules each of histone H2A, H2B, H3 and H4. The DNA entering and exiting the particle may be bound by the linker histone H1. Whereas deposition of bulk histones is confined to S-phase, paralogs of the common histones, known as histone variants, are available to carry out functions throughout the cell cycle and accumulate in post-mitotic cells. Histone variants confer different structural properties on nucleosomes by wrapping more or less DNA or by altering nucleosome stability. They carry out specialized functions in DNA repair, chromosome segregation and regulation of transcription initiation, or perform tissue-specific roles. In this Cell Science at a Glance article and the accompanying poster, we briefly examine new insights into histone origins and discuss variants from each of the histone families, focusing on how structural differences may alter their functions.

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Primary Role of the Nucleosome

Cited by 130 publications

References 74 publications

Asymmetry in histone rotation in forced unwrapping and force quench rewrapping in a nucleosome

Asymmetry in histone rotation in forced unwrapping and force quench rewrapping in a nucleosome

Understanding transcription across scales: From base pairs to chromosomes

Histone variants at a glance

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