Kikue Tachibana-Konwalski

Molecular control of the oocyte-to-zygote transition

  • Fertilization transforms two highly differentiated cells, egg and sperm, into a single totipotent cell—the zygote—with the potential to give rise to a complete organism.  Female germ cells called oocytes undergo two rounds of meiotic chromosome segregation to produce haploid eggs.  The oocyte-to-zygote transition occurs in the absence of transcription and involves global changes in protein synthesis and degradation.  Zygote formation involves a dramatic reorganization of sperm chromatin by factors stored in the oocyte.  How chromatin is assembled and reprogrammed after fertilization remain crucial questions in biology.

    Our group aims to define the molecular events driving the mammalian oocyte-to-zygote transition and to understand how age-dependent deterioration of these mechanisms impacts fertility.  We focus on the switch from the meiotic to the mitotic cell cycle machinery at fertilization and maternal control of sperm chromatin reorganization.  Inside the newly formed zygote, sperm chromatin decondenses, protamines are exchanged for histones, a pronucleus is formed and chromatin remodeling erases cell-type specific epigenetic marks as part of the natural reprogramming that occurs during the first embryonic cell cycle.  We are investigating factors required for these processes using a combination of mouse molecular genetics, biochemistry, TEV protease technology and live-cell microscopy.

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Selected Publications

Flyamer, IM., Gassler, J., Imakaev, M., Brandão, HB., Ulianov, SV., Abdennur, N., Razin, SV., Mirny, LA., Tachibana-Konwalski, K. (2017). Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition. Nature. 544(7648):110-114 (abstract)
Burkhardt, S., Borsos, M., Szydlowska, A., Godwin, J., Williams, SA., Cohen, PE., Hirota, T., Saitou, M., Tachibana-Konwalski, K. (2016). Chromosome Cohesion Established by Rec8-Cohesin in Fetal Oocytes Is Maintained without Detectable Turnover in Oocytes Arrested for Months in Mice. Curr Biol. 26(5):678-85 (abstract)
Ladstätter, S., Tachibana-Konwalski, K. (2016). A Surveillance Mechanism Ensures Repair of DNA Lesions during Zygotic Reprogramming. Cell. 167(7):1774-1787.e13 (abstract)
Zou, L. (2016). A Zygotic Checkpoint for Unrepaired Lesions. Cell. 167(7):1676-1678 (abstract)
Tachibana-Konwalski, K., Godwin, J., Borsos, M., Rattani, A., Adams, DJ., Nasmyth, K. (2013). Spindle assembly checkpoint of oocytes depends on a kinetochore structure determined by cohesin in meiosis I. Curr Biol. 23(24):2534-9 (abstract)
Seitan, VC., Hao, B., Tachibana-Konwalski, K., Lavagnolli, T., Mira-Bontenbal, H., Brown, KE., Teng, G., Carroll, T., Terry, A., Horan, K., Marks, H., Adams, DJ., Schatz, DG., Aragon, L., Fisher, AG., Krangel, MS., Nasmyth, K., Merkenschlager, M. (2011). A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation. Nature. 476(7361):467-71 (abstract)
Tachibana-Konwalski, K., Godwin, J., van der Weyden, L., Champion, L., Kudo, NR., Adams, DJ., Nasmyth, K. (2010). Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes. Genes Dev. 24(22):2505-16 (abstract)
Gonzalez, MA., Tachibana, KE., Adams, DJ., van der Weyden, L., Hemberger, M., Coleman, N., Bradley, A., Laskey, RA. (2006). Geminin is essential to prevent endoreduplication and to form pluripotent cells during mammalian development. Genes Dev. 20(14):1880-4 (abstract)

In reference to Spindle Assembly Checkpoint of Oocytes Depends on a Kinetochore Structure Determined by Cohesin in Meiosis I. Curr Biol., 2013
see also Dispatch in Current Biology, Volume 23, Issue 24: Meiosis: Cohesin's Hidden Role in the Checkpoint Revealed

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