Heterochromatin loss results in abnormal nuclear morphology, which is a hallmark of human disease ( Stephens et al., 2019a Uhler and Shivashankar, 2018). Heterochromatin is the stiff, compact, and gene-poor form of chromatin. IntroductionĬhromatin, which fills the nucleus, is a repository of information, but it is also a physical element that provides structure, mechanical rigidity, shape, and function to the nucleus. 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. In mitotic chromosomes, HP1α similarly bolsters stiffness while aiding in mitotic alignment and faithful segregation. 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. Single-nucleus micromanipulation reveals that HP1α is essential to chromatin-based mechanics and maintains nuclear morphology, separate from histone methylation. Degradation did not alter transcription, local chromatin compaction, or histone methylation, but did decrease chromatin stiffness. We used a novel HP1α auxin-inducible degron human cell line to rapidly degrade HP1α. Heterochromatic histone methylation controls nucleus and chromosome stiffness, but the contribution of heterochromatin protein HP1α (CBX5) is unknown. Department of Physics and Astronomy, Northwestern University, United States Ĭhromatin, which consists of DNA and associated proteins, contains genetic information and is a mechanical component of the nucleus.The Fred Hutchinson Cancer Research Center, United States.Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, United States Biology Department, University of Massachusetts Amherst, United States.Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, United States.Institute for Medical Engineering and Science and Department of Physics, Massachusetts Institute of Technology, United States.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. Archives
January 2023
Categories |