Title:
Elucidation of the structure and function of heterochromatin through HP1 binding proteins

 

Speaker:
Chikashi OBUSE
Osaka University, Graduate School of Science, Department of Biological Sciences

 

Abstract:
Heterochromatin is a condensed chromatin structure throughout the cell cycle and is thought to be involved in the regulation of transcription. The main component of heterochromatin, HP1, recognizes the histone H3 methylated at 9th lysine (H3K9me) and is involved in various chromatin functions through various binding proteins.

To understand the structure and function of heterochromatin at the molecular level, we identified 82 human HP1-binding proteins by comprehensive proteomic approach (1). Through the studies of these HP1-binding proteins; for example, a mechanism of orientation of the kinetocore complex that is essential for chromosome segregation (2, 3), a mechanism for controlling the localization and activity of Aurora B kinase that is essential for M phase progression (1), and a mechanism for pathway choice whether DNA damage is repaired by homologous recombination or non-homologous end joining (NHEJ) (4), show that HP1 turned out to be a protein which assists the localization and function of various functional chromatin complexes appropriately. Furthermore, we uncovered HP1 was also clarified as a protein which is involved in condensation of heterochromatin in inactive X chromosome (5), indicating a way how so-called epigenetic marks such as histone marks and non-coding RNAs are converted into higher-order chromatin structures. In addition, various histone modifying enzymes interact with HP1, and this network is thought to contribute to the maintenance and conversion of epigenetic marks and chromatin conformation.

In this seminar, I will show an approach that combines systematic proteomics and genomics analysis of HP1 and its binding proteins, which allow us understanding the structure and function of heterochromatin.

 

References:
1) Nozawa R.S., Nagao K., Masuda H.T., Iwasaki O., Hirota T., Nozaki N., Kimura H., Obuse C. (2010) Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation. Nature Cell Biol., 12, 719-727.
2) Obuse, C., Iwasaki, O., Kiyomitsu, T., Goshima, G., Toyoda, Y. and Yanagida, M. (2004) A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nature Cell Biol., 6, 1135-1141.
3) Kiyomitsu T., Iwasaki O., Obuse C., Yanagida M.(2010) Inner centromere formation requires hMis14, a trident kinetochore protein that specifically recruits HP1 to human chromosomes. J. Cell. Biol., 188, 791-807.
4) Isobe S.Y, Nagao K, Nozaki N, Kimura H, Obuse C. (2017) Inhibition of RIF1 by SCAI Allows BRCA1-Mediated Repair. Cell Rep., 20, 297-307.
5) Nozawa R.S., Nagao K., Igami K.T., Shibata S., Shirai N., Nozaki N., Sado T., Kimura H., Obuse C. (2013) Human inactive X chromosome is compacted through a polycomb-independent SMCHD1-HBiX1 pathway. Nature Struct. Mol. Biol., 20, 566-573.