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HP1α is a Chromatin Crosslinker That Controls Nuclear and Mitotic Chromosome Mechanics
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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 HP1 alpha (CBX5) is unknown. We used a novel HP1 alpha auxin-inducible degron human cell line to rapidly degrade HP1 alpha. Degradation did not alter transcription, local chromatin compaction, or histone methylation, but did decrease chromatin stiffness. Single-nucleus micromanipulation reveals that HP1 alpha is essential to chromatin-based mechanics and maintains nuclear morphology, separate from histone methylation. Further experiments with dimerization-deficient HP1 alpha(I)(165E) indicate that chromatin crosslinking via HP1 alpha dimerization is critical, while polymer simulations demonstrate the importance of chromatin-chromatin crosslinkers in mechanics. In mitotic chromosomes, HP1 alpha similarly bolsters stiffness while aiding in mitotic alignment and faithful segregation. HP1 alpha is therefore a critical chromatin-crosslinking protein that provides mechanical strength to chromosomes and the nucleus throughout the cell cycle and supports cellular functions.
Type
article
article
article
Date
2021-01-01
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License
UMass Amherst Open Access Policy
License
http://creativecommons.org/licenses/by/4.0/