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
KeywordsCell Line, Cell Nucleus, Chromatin, Chromobox Protein Homolog 5, Chromosomal Proteins, Non-Histone, Chromosomes, Humans, Methylation, Mitosis
Abstract

<p>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 HP1α 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.</p>

DOI10.7554/eLife.63972
Alternate JournalElife
PubMed ID34106828
PubMed Central IDPMC8233041
Grant ListU01 CA200060 / CA / NCI NIH HHS / United States
R01 HG009906 / HG / NHGRI NIH HHS / United States
U01 DA040583 / DA / NIDA NIH HHS / United States
R35 GM124820 / GM / NIGMS NIH HHS / United States
R01 GM105847 / GM / NIGMS NIH HHS / United States
U01 DA040601 / DA / NIDA NIH HHS / United States
UM1 HG011536 / HG / NHGRI NIH HHS / United States
U54 DK107980 / DK / NIDDK NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
R00 GM123195 / GM / NIGMS NIH HHS / United States
R24 DK106766 / DK / NIDDK NIH HHS / United States
U54 CA193419 / CA / NCI NIH HHS / United States