FBS Colloquia No.170Laboratory of Chromosome Biology
Seminar or Lecture |
Epigenetic regulation for kinetochore assembly in vertebrate cells Tetsuya Hori [Laboratory of Chromosome Biology] Kinetochore protein interaction network Masatoshi Hara [Laboratory of Chromosome Biology] |
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Date and Time | Wednesday, October 4, 2017, 12:15-13:00 |
Place | 2F Seminar room, BioSystems Building |
Contact |
Tetsuya Hori |
Epigenetic regulation for kinetochore assembly in vertebrate cells
The centromere is an essential genome region where the kinetochore is established for faithful chromosome segregation. In most organisms, centromeres are specified by sequence-independent epigenetic mechanisms through the deposition of the centromere-specific histone H3-variant CENP-A. Following centromere specification, multiple kinetochore proteins are assembled on centromeres. However, it remains unknown how additional epigenetic regulation is involved in centromere specification and kinetochore assembly. To address the question, we have been analyzing histone modifications to find additional epigenetic features of centromeric chromatin. Previously, we experimentally isolated neocentromere-containing chicken DT40 cell lines. We utilized the non-repetitive nature of neocentromeres combined with extensive ChIP-seq analyses with antibodies against various histone modifications and found several histone modifications accumulated at centromeres. Here, I demonstrate recent progress on these analyses and discuss about how centromeres are specified and kinetochore assembly occurs through epigenetic regulation in vertebrate cells.
Kinetochore protein interaction network
Mitosis is a critical process during cell cycle in which chromosomes drastically change their shapes and move into the daughter cells, assuring accurate transmission of the genetic materials to the next generations. Failure of the process can lead to chromosome mis-segregation, which causes many diseases including cancer. The faithful chromosome segregation requires kinetochore, a large protein complex consisting of more than hundred proteins in vertebrate, which is formed at centromere region on each chromosome, to attach to spindle microtubules. Among kinetochore proteins, CCAN (Constitutive Centromere Associated Network) proteins including 16 subunits and KMN (Knl1, Mis12 and Ndc80 complexes) network proteins form core architecture in vertebrate kinetochores. The CCAN proteins constitutively localize to centromere throughout the cell cycle and the KMN network proteins are recruited to the CCAN proteins during M-phase to establish a functional kinetochore that binds to microtubules. In the talk, I'd like to discuss our recent studies, which led us to revisit a widely-accepted model for kinetochore protein interactions in mitosis.