Hp1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics

Amy R. Strom, Ronald J. Biggs, Edward J. Banigan, Xiaotao Wang, Katherine Chiu, Cameron Herman, Jimena Collado, Feng Yue, Joan C.Ritland Politz, Leah J. Tait, David Scalzo, Agnes Telling, Mark Groudine, Clifford P. Brangwynne, John F. Marko, Andrew D. Stephens

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Article numbere63972
JournaleLife
Volume10
DOIs
StatePublished - Jun 2021

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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