Hp1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics
Amy R. Strom,Ronald J Biggs,Edward J. Banigan,Xiaotao Wang,Katherine Chiu,Cameron Herman,Jimena Collado,Feng Yue,Joan C. Ritland Politz,Leah J Tait,David Scalzo,Agnes Telling,Mark Groudine,Clifford P. Brangwynne,John F. Marko,Andrew D. Stephens +15 more
TLDR
In this paper, the authors used a novel HP1α auxin-inducible degron human cell line to rapidly degrade HP 1α (CBX5) and found that HP 1 α is essential to chromatin-based mechanics and maintains nuclear morphology.Abstract:
Chromatin, which consists of DNA and associated proteins, contains genetic information and is a mechanical component of the nucleus. Heterochromatic histone methylation controls nucleus and chromosome stiffness, but the contribution of heterochromatin protein HP1α (CBX5) is unknown. We used a novel HP1α auxin-inducible degron human cell line to rapidly degrade HP1α. Degradation did not alter transcription, local chromatin compaction, or histone methylation, but did decrease chromatin stiffness. Single-nucleus micromanipulation reveals that HP1α is essential to chromatin-based mechanics and maintains nuclear morphology, separate from histone methylation. Further experiments with dimerization-deficient HP1αI165E indicate that chromatin crosslinking via HP1α dimerization is critical, while polymer simulations demonstrate the importance of chromatin-chromatin crosslinkers in mechanics. In mitotic chromosomes, HP1α similarly bolsters stiffness while aiding in mitotic alignment and faithful segregation. HP1α is therefore a critical chromatin-crosslinking protein that provides mechanical strength to chromosomes and the nucleus throughout the cell cycle and supports cellular functions.read more
Citations
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Mechanics and functional consequences of nuclear deformations
TL;DR: In this article , the physical connections from chromatin to nuclear lamina and cytoskeletal filaments are considered as a single mechanical unit, and a critical review of the structural and functional adaptive responses of the nucleus to deformations is provided.
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Interplay between chromatin marks in development and disease.
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The solid and liquid states of chromatin.
TL;DR: A comprehensive review of the 60 years history of chromatin aggregation studies is presented in this paper, where the authors highlight the recent findings that under specific solution conditions chromatin can undergo liquid-liquid phase separation (LLPS) rather than LSPS.
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Force generation by protein-DNA co-condensation
Thomas Quail,Stefan Golfier,Maria Elsner,Keisuke Ishihara,Vasanthanarayan Murugesan,Roman Renger,Frank Jülicher,Frank Jülicher,Jan Brugués +8 more
TL;DR: The findings show that DNA condensation mediated by transcription factors could bring distant regions of DNA into close proximity, suggesting that this physical mechanism is a possible general regulatory principle for chromatin organization that may be relevant in vivo.
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Liquid–liquid phase separation in tumor biology
TL;DR: In this article , the authors comprehensively summarize the detailed mechanisms of biomolecular condensate formation and biophysical function and review the recent major advances toward elucidating the multiple mechanisms involved in cancer cell pathology driven by aberrant liquid-liquid phase separation (LLPS).
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