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SUMMARY:Epigenetic reprogramming in mammalian development - Professor Wolf
  Reik\, The Babraham Institute\, Cambridge
DTSTART:20090929T103000Z
DTEND:20090929T110000Z
UID:TALK18686@talks.cam.ac.uk
CONTACT:Hannah Critchlow
DESCRIPTION:This talk is part of the Cambridge Clinical Neuroscience and M
 ental Health Symposium\, 29th - 30th September 2009 at West Road Concert H
 all. This event is free to attend for cambridge neuroscientists although r
 egistration is required. To register\, and for further information\, pleas
 e visit: http://www.neuroscience.cam.ac.uk/cnmhs/\n\nAbstract: We study ep
 igenetic mechanisms of gene regulation and their impact in mammalian devel
 opment. Long noncoding RNAs play important roles in imprinting\, including
  potentially in regulating gene expression and physiology of networks of i
 mprinted genes. We have found that the imprinted long noncoding RNA H19 is
  the most conserved regulatory noncoding RNA in mammalian evolution\, and 
 may have a function in fine tuning growth. The imprinted long noncoding RN
 A Kcnq1ot1\, by contrast\, targets epigenetic gene silencing in cis to a g
 enomic region which is 1 Megabase in size. We have found that this RNA is 
 localised to the nucleus where it ‘coats’ the chromosome region it ina
 ctivates. \n\nEpigenetic reprogramming occurs in early embryos and in prim
 ordial germ cells\, and is important for imprinting\, pluripotency of the 
 embryonic and germ cell genome\, and for the erasure of epimutations. We a
 re carrying out genome-wide screens for DNA methylation\, and comparing se
 veral pluripotent and more differentiated cell types\, in order to underst
 and the extent of methylation reprogramming and what sequences are regulat
 ed by it. We have recently carried out genome-wide Bisulphite-Seq in primo
 rdial germ cells\, which has revealed the extent of reprogramming on an un
 precedented scale. \n\nWe have also begun to test the hypothesis that epig
 enetic regulation is important for lineage commitment and its stability. W
 e identified a trophoblast transcription factor\, Elf5\, that is methylate
 d and repressed in ES cells\, but unmethylated and expressed in TS cells. 
 Expression of this transcription factor sustains a positive feedback loop 
 between key trophoblast fate determinants\, and is thus necessary for trop
 hoblast commitment. By contrast\, epigenetic silencing of this trophoblast
  determinant in the epiblast lineage disrupts the feedback loop so that tr
 ophoblast cell fate is aborted should it initially take place. This type o
 f epigenetically regulated feedback loop appears to ensure initial plastic
 ity followed by canalization of lineage fate. \n\nReferences: \n\nSmits et
  al Nature Genetics 40\, 971-976 (2008)\nNg et al Nature Cell Biology 10\,
  1280-1290 (2008)\nPonting et al Cell 136\, 629-641 (2009)\n\n\n\nBiograph
 y: Wolf Reik is Associate Director of Research and Head of the Laboratory 
 of Developmental Genetics and Imprinting at the Babraham Institute in Camb
 ridge. After receiving his MD from the Universities of Freiburg and Hambur
 g in Germany\, he went on to study for his postgraduate degree with Rudolf
  Jaenisch (on retroviruses\, epigenetics\, DNA methylation) before underta
 king postdoctoral work with Azim Surani (on genomic imprinting) in Cambrid
 ge as an EMBO Fellow. He was a Fellow of the Lister Institute of Preventiv
 e Medicine\, and headed the Programme of Developmental Genetics at the Bab
 raham Institute before taking up his current post as Associate Director of
  the Institute. He has a joint appointment on the board of management of t
 he Centre for Trophoblast Research at the University of Cambridge\, and as
  Professor of Epigenetics in the Department of Physiology\, Development\, 
 and Neuroscience. \n\nWolf Reik’s research interests are in genomic impr
 inting and in epigenetic mechanisms of gene regulation in early embryos\, 
 germ cells\, and stem cells\, and in particular in the role of epigenetic 
 reprogramming in developmental plasticity. He has published more than 140 
 research papers\, and received a number of prizes and distinctions for his
  work\, including the Wellcome Prize of Physiology. He is an elected membe
 r of EMBO and a Fellow of the Academy of Medical Sciences. He has served o
 n several national and international academic boards and is currently a me
 mber of the Cancer Research UK Science Funding Committee. He is a member o
 f editorial boards of several academic journals and of Faculty 1000. He al
 so sits on the Executive Board of The Epigenome EU Network of Excellence\,
  is a consultant to CellCentric\, Cambridge\, and on the Scientific Adviso
 ry Board\, Center for Genomic Regulation\, Barcelona. \n
LOCATION:West Road Concert Hall
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