BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:"\;Pioneer Transcription factors in programming and reprogramm ing"\; - Dr Abdenour Soufi\; MRC Centre for Regenerative Medicine\, U niversity of Edinburgh DTSTART:20170601T120000Z DTEND:20170601T130000Z UID:TALK70949@talks.cam.ac.uk CONTACT:Bobbie Claxton DESCRIPTION:Abdenour Soufi is a Chancellor’s fellow at the MRC Centre fo r Regenerative Medicine and the Institute for Stem Cell Research at the Un iversity of Edinburgh. He has obtained a PhD degree in Biophysics from the University of Bristol. Abdenour did his postdoctoral studies with Prof Ke nneth Zareth at the University of Pennsylvania\, U.S.A. where he performed seminal work on the transcriptional control of reprogramming tissue cells to become stem cells (iPS). He was the first to propose that transcriptio n factors act as pioneer factors during iPS reprogramming (Soufi et al.\, 2012 Cell\, Soufi et al.\, 2015 Cell). His research is focused on revealin g how chromatin structure controls cellular identity. Abdenour has recentl y received an MRC career development award to engineer synthetic factors t hat are more potent in cellular reprogramming.\n\nAbstract:\n\nIt is astou nding to discover that it takes so few transcription factors (TFs) to conv ert cells from one type to another. Strikingly\, the four TFs: Oct4\, Sox2 \, Klf4\, and c-Myc (OSKM) are able to convert fibroblasts to become induc ed pluripotent stem cells (iPSCs)\, which are highly similar to embryonic stem cells (ESCs). However this reprogramming process is highly inefficien t and often results in partially reprogrammed cells. To understand how OSK M initially target silent pluripotency genes\, we previously mapped the in teraction of OSKM with the somatic genome early in reprogramming. We found that O\, S\, and K\, but not Myc\, engage closed chromatin at distal site s\, a hallmark of pioneer activity. We have also investigated the differen tial interaction of O\, S\, K\, and M with nucleosomes\, both in vitro and in vivo\, revealing that the pioneer activity of reprogramming factors re lates to the basic ability of TFs to adapt their DNA-binding domains (DBDs ) to target partial motifs exposed on the surface of nucleosomes. Other DB Ds that lack such adaptability can bind with pioneer factors to recognize degenerate motifs on nucleosomes. Together our data provide the molecular basis by which pioneer factors interact with nucleosomes to engage silent chromatin\, endowing competence for subsequent gene activation.\n LOCATION:Babraham - The Brian Heap Seminar Room END:VEVENT END:VCALENDAR