TY - JOUR TI - HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics AU - Strom, Amy R AU - Biggs, Ronald J AU - Banigan, Edward J AU - Wang, Xiaotao AU - Chiu, Katherine AU - Herman, Cameron AU - Collado, Jimena AU - Yue, Feng AU - Ritland Politz, Joan C AU - Tait, Leah J AU - Scalzo, David AU - Telling, Agnes AU - Groudine, Mark AU - Brangwynne, Clifford P AU - Marko, John F AU - Stephens, Andrew D A2 - Narlikar, Geeta J A2 - Struhl, Kevin A2 - Redding, Sy VL - 10 PY - 2021 DA - 2021/06/09 SP - e63972 C1 - eLife 2021;10:e63972 DO - 10.7554/eLife.63972 UR - https://doi.org/10.7554/eLife.63972 AB - 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. KW - nucleus KW - heterochromatin KW - HP1a KW - mechanics KW - mitosis KW - chromosome JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -