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HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | eLife Sciences Publications Ltd 2021-06-01 |
Deskripsi
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.