The spatiotemporal dynamics of chromatin protein HP1alpha is essential for accurate chromosome segregation during cell division [DNA and Chromosomes]

August 7th, 2014 by Chu, L., Huo, Y., Liu, X., Yao, P., Thomas, K., Jiang, H., Zhu, T., Zhang, G., Chaudhry, M., Adams, G., Thompson, W., Zhen, D., Jin, C., He, P., Yao, X.

Heterochromatin protein 1 alpha (HP1a) is involved in regulation of chromatin plasticity, DNA damage repair and centromere dynamics. HP1a reads histone di-methylation and tri-methylation of Lys9 via its chromo domain. HP1a is localized to heterochromatin in interphase cells but liberated from chromosomal arm at the onset of mitosis. The structure determinants required for HP1a localization in interphase and the regulation of HP1a dynamics have remained elusive. Here we show that centromeric localization of HP1a depends on SUV39H1 activity in interphase but not in mitotic cells. HP1a begins liberating from chromsomal arms in early mitosis. To test the role of this dissociation, we engineered a HP1a construct that persistently localizes to chromsomal arms. We show that the persistent localization of HP1a to chromsomal arms is sufficient for kinetochore-microtubule attachment perturbation by relocating chromosome passenger complex (CPC) and Sgo1 from centromeres to chromsomal arms, which prevents sister chromatids resolution. Our further analyses show that Mis14 and perhaps other PxVxL-containing proteins determine the localization of HP1a to centromere in mitosis. Together, our data suggest a model in which spatiotemporal dynamics of HP1a localization to centromere is governed by two distinct structural determinants. These findings reveal a previously unrecognized but essential link between HP1a-interacting molecular dynamics and chromosome plasticity in accurate cell division.
  • Posted in Journal of Biological Chemistry, Publications
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