HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics
- Princeton University, United States
- Northwestern University, United States
- Massachusetts Institute of Technology, United States
- Feinberg School of Medicine, Northwestern University, United States
- University of Massachusetts Amherst, United States
- The Fred Hutchinson Cancer Research Center, United States
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 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.
Data availability
We have provided the RNAseq data sets in the supplemental material as excel files
Article and author information
Author details
Clifford P Brangwynne
Funding
National Institutes of Health (U54DK107980)
- John F Marko
National Institutes of Health (U01DA040583)
- Mark Groudine
National Institutes of Health (1UM1HG011536)
- John F Marko
- Andrew D Stephens
National Institutes of Health (R00GM123195)
- Andrew D Stephens
National Institutes of Health (U54CA193419)
- John F Marko
National Institutes of Health (U01 DA040601)
- Clifford P Brangwynne
Mark Foundation For Cancer Research (Life science research foundation Postdoctoral Fellowship,AWD1006303)
- Amy R Strom
National Institutes of Health (GM114190)
- Edward J Banigan
National Institutes of Health (R24DK106766)
- Feng Yue
National Institutes of Health (1R35GM124820)
- Feng Yue
National Institutes of Health (R01HG009906)
- Feng Yue
National Institutes of Health (U01CA200060)
- Feng Yue
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Geeta J Narlikar, University of California, San Francisco, United States
Version history
- Received: October 12, 2020
- Accepted: June 8, 2021
- Accepted Manuscript published: June 9, 2021 (version 1)
- Version of Record published: June 25, 2021 (version 2)
Copyright
© 2021, Strom et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics
eLife 10:e63972.
https://doi.org/10.7554/eLife.63972
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