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HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics

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...

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Detalles Bibliográficos
Autores principales: Strom, Amy R, Biggs, Ronald J, Banigan, Edward J, Wang, Xiaotao, Chiu, Katherine, Herman, Cameron, Collado, Jimena, Yue, Feng, Ritland Politz, Joan C, Tait, Leah J, Scalzo, David, Telling, Agnes, Groudine, Mark, Brangwynne, Clifford P, Marko, John F, Stephens, Andrew D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233041/
https://www.ncbi.nlm.nih.gov/pubmed/34106828
http://dx.doi.org/10.7554/eLife.63972
Descripción
Sumario: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.