HP1[alpha] is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics

• Published in: eLife 2021-06, Vol.10
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Cells; Chromatin; Chromosomes; Crosslinked polymers; Methylation
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.63972

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].sup.I165E 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.