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

eLife

Andrew D Stephens¹  Katherine Chiu¹  Xiaotao Wang²  Feng Yue³  Ronald J Biggs⁴  Jimena Collado⁴  Cameron Herman⁴  John F Marko⁵  Amy R Strom⁶  Clifford P Brangwynne⁶  Edward J Banigan⁷  Joan C Ritland Politz⁸  Mark Groudine⁸  David Scalzo⁸  Agnes Telling⁸  Leah J Tait⁸ 

[1] Biology Department, University of Massachusetts Amherst, Amherst, United States;Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, United States;Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, United States;Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, United States;Department of Molecular Biosciences, Northwestern University, Evanston, United States;Department of Molecular Biosciences, Northwestern University, Evanston, United States;Department of Physics and Astronomy, Northwestern University, Evanston, United States;Howard Hughes Medical Institute, Department of Chemical and Biological Engineering, Princeton University, Princeton, United States;Institute for Medical Engineering and Science and Department of Physics, Massachusetts Institute of Technology, Cambridge, United States;The Fred Hutchinson Cancer Research Center, Seattle, United States;

关键词: nucleus;    heterochromatin;    HP1a;    mechanics;    mitosis;    chromosome;    Human;   

DOI  :  10.7554/eLife.63972

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY