Job Opening for Nucleosome Mechanic: Flexibility Required

Abstract

The nucleus has been studied for well over 100 years, and chromatin has been the intense focus of experiments for decades. In this review, we focus on an understudied aspect of chromatin biology, namely the chromatin fiber polymer's mechanical properties. In recent years, innovative work deploying interdisciplinary approaches including computational modeling, in vitro manipulations of purified and native chromatin have resulted in deep mechanistic insights into how the mechanics of chromatin might contribute to its function. The picture that emerges is one of a nucleus that is shaped as much by external forces pressing down upon it, as internal forces pushing outwards from the chromatin. These properties may have evolved to afford the cell a dynamic and reversible force-induced communication highway which allows rapid coordination between external cues and internal genomic function.

Centromeric Transcription: A Conserved Swiss-Army Knife

“…It is interesting to speculate that the role of histone chaperones go beyond assisting histone localization and nucleosomes dynamics [ 181 ]. Maybe, histone chaperones function as a critical factor contributing to chromatin domain formation, long-distance chromatin interactions, and even mechanosensing [ 182 ] by bringing together nucleosomes, non-coding RNAs, and other chromatin binding factors. Consequently, misregulation would lead to a broad range of chromatin effects, which are commonly observed in cancers.…”

“…At the inner centromere, CPC is localized and activated through centromeric transcription during mitosis. Another unanswered question is whether centromeric transcription is sensitive to mitotic pulling forces ( Figure 3 D), potentially linking mitotic biomechanical events to direct transcriptional outputs [ 182 ]. In cancers, ectopic CENP-A nucleosomes are commonly found, yet it remains unclear how precisely CENP-A is recruited to these sites.…”

Mechanical properties of nucleoprotein complexes determined by nanoindentation spectroscopy

“…Macromolecular structures produce mechanical force properties such as elasticity, viscosity, and thermal motion, which are important [59]. Chromatin fibers possess unique mechanical properties that contribute to its function [60]. Herein, we describe adaptations of our recently developed single-molecule nanoindentation tools [18] applied to bulk chromatin purified from human cells.…”