title: Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming.
abstract: Nuclear transfer to oocytes is an efficient way to transcriptionally reprogram somatic nuclei, but its mechanisms remain unclear. Here, we identify a sequence of molecular events that leads to rapid transcriptional reprogramming of somatic nuclei after transplantation to Xenopus oocytes. RNA-seq analyses reveal that reprogramming by oocytes results in a selective switch in transcription toward an oocyte rather than pluripotent type, without requiring new protein synthesis. Time-course analyses at the single-nucleus level show that transcriptional reprogramming is induced in most transplanted nuclei in a highly hierarchical manner. We demonstrate that an extensive exchange of somatic- for oocyte-specific factors mediates reprogramming and leads to robust oocyte RNA polymerase II binding and phosphorylation on transplanted chromatin. Moreover, genome-wide binding of oocyte-specific linker histone B4 supports its role in transcriptional reprogramming. Thus, our study reveals the rapid, abundant, and stepwise loading of oocyte-specific factors onto somatic chromatin as important determinants for successful reprogramming.
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.
authors: Jerome
authors: J
authors: Jullien
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.
authors: Kei
authors: K
authors: Miyamoto
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.
authors: Vincent
authors: V
authors: Pasque
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.
authors: George E
authors: GE
authors: Allen
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.
authors: Charles R
authors: CR
authors: Bradshaw
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.
authors: Nigel J
authors: NJ
authors: Garrett
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.
authors: Richard P
authors: RP
authors: Halley-Stott
authors: Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan.
authors: Hiroshi
authors: H
authors: Kimura
authors: Laboratory of Molecular Genetics, Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8602, Japan.
authors: Keita
authors: K
authors: Ohsumi
authors: Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK. Electronic address: j.gurdon@gurdon.cam.ac.uk.
authors: John B
authors: JB
authors: Gurdon
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics* / Q000502:physiology; D002843:Chromatin / Q000378:metabolism*; D016678:Genome; D006657:Histones / Q000502:physiology*; D051379:Mice; D053652:Nuclear Transfer Techniques; D009865:Oocytes / Q000378:metabolism*; D009928:Organ Specificity; D012313:RNA / Q000235:genetics; D017423:Sequence Analysis, RNA; D014981:Xenopus / Q000196:embryology* / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D012313:RNA