John Gurdon Kt DPhil DSc FRS, Distinguished Group Leader, Nobel Laureate in Physiology or Medicine 2012, member of the Department of Zoology.
Nuclear reprogramming by oocytes and eggs
Can we make cell reprogramming more efficient? When a sperm nucleus enters the egg at fertilisation, factors in the egg cytoplasm initiate a sequence of gene expression events from the combined egg and sperm DNA that kick-start development of a new organism.
When the nucleus of a mature body cell is transplanted to an egg, it is similarly induced to change its pattern of gene expression to that of an embryo. Yet most body cells resist making this change, while almost all sperm nuclei are successfully reprogrammed.
Our research aims to characterise the fine details of cell reprogramming: how the oocyte reprogrammes a cell nucleus. Equally importantly, we want to know what mechanisms ensure the remarkable stability of normal cell differentiation and its resistance to reprogramming by eggs.
We use a variety of techniques for manipulating gene expression before maternal reprogramming factors become active in defolliculated oocytes, including: adding different transcription factors, chromatin fractionation, over- and under- expressing messenger RNA and mutating donor nuclei.
• Marta Teperek et al. (2016) Sperm is epigenetically programmed to regulate gene transcription in embryos. Genome Research (Published online March 31; doi:10.1101/gr.201541.115)
• Koziol MJ, Bradshaw CR, Allen GE, Costa AS, Frezza C, Gurdon JB. (2016) Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat Struct Mol Biol 23(1):24-30.
• Jullien J et al. (2014) Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming. Molecular Cell 55: 1–13.
• Miyamoto K et al.(2013) Nuclear WAVE1 is required for reprogramming transcription in oocytes and for normal development. Science 341: 1002– 1005.
• Jullien J, Astrand C, Szenker E, Garrett N, Almouzni G and Gurdon JB (2012) HIRA dependent H3.3 deposition is required for transcriptional reprogramming following nuclear transfer to Xenopus oocytes. Epigenetics and Chromatin, 5:17
• Narbonne P, Miyamoto K and Gurdon JB (2012) Reprogramming and development in nuclear transfer embryos and in interspecific systems. Current Opinion in Genetics & Development, 22:450-458
• Pasque V, Jullien J, Miyamoto K, Halley-Stott RP and Gurdon JB (2011) Genetic and epigenetic factors affecting nuclear reprogramming efficiency. Trends in Genetics, 27(12)516-525
• Gurdon JB (2006) From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation. Ann Rev Cell Dev Biol 22, 1-22. PMID: 16704337