Year: 2020
Type: preprint
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 HP1α I165E 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.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Visualization, modeling and validation of chromatin interaction data, Optogenetic Droplets: Using Light to Control Nucleoplasmic Phase Separation, The WashU 4DN Network Data Coordination and Integration Center, Analyzing the role of chromatin compaction in nuclear mechanics, structure, and function, G9000085267, G9000108312, G9000259701, G9000270135, G9000320333
OpenAlex ID: W3091820689