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

TitleHP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics.
Publication TypeJournal Article
Year of Publication2021
AuthorsStrom, AR, Biggs, RJ, Banigan, EJ, Wang, X, Chiu, K, Herman, C, Collado, J, Yue, F, Politz, JCRitland, Tait, LJ, Scalzo, D, Telling, A, Groudine, M, Brangwynne, CP, Marko, JF, Stephens, AD
JournalElife
Volume10
Date Published2021 Jun 09
ISSN2050-084X
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.

DOI10.7554/eLife.63972
Alternate JournalElife
PubMed ID34106828
PubMed Central IDPMC8233041
Grant ListU54DK107980 / NH / NIH HHS / United States
U01DA040583 / NH / NIH HHS / United States
1UM1HG011536 / NH / NIH HHS / United States
R00GM123195 / NH / NIH HHS / United States
U54CA193419 / NH / NIH HHS / United States
U01 DA040601 / NH / NIH HHS / United States
Life science research foundation Postdoctoral Fellowship,AWD1006303 / / Mark Foundation For Cancer Research /
GM114190 / NH / NIH HHS / United States
R24DK106766 / NH / NIH HHS / United States
1R35GM124820 / NH / NIH HHS / United States
R01HG009906 / NH / NIH HHS / United States
U01CA200060 / NH / NIH HHS / United States
Life science research foundation Postdoctoral Fellowship / / Mark Foundation For Cancer Research /
AWD1006303 / / Mark Foundation For Cancer Research /
U01 DA040601 / NH / NIH HHS / United States
GM114190 / NH / NIH HHS / United States
U54DK107980 / NH / NIH HHS / United States
U54CA193419 / NH / NIH HHS / United States
R24DK106766 / NH / NIH HHS / United States
1R35GM124820 / NH / NIH HHS / United States
R01HG009906 / NH / NIH HHS / United States
U01CA200060 / NH / NIH HHS / United States
U01DA040583 / NH / NIH HHS / United States
1UM1HG011536 / NH / NIH HHS / United States
R00GM123195 / NH / NIH HHS / United States