Hierarchical Molecular Events Driven by Oocyte-Specific Factors Lead to Rapid and Extensive Reprogramming

Autor: Jullien, Jerome, Miyamoto, Kei, Pasque, Vincent, Allen, George E., Bradshaw, Charles R., Garrett, Nigel J., Halley-Stott, Richard P., Kimura, Hiroshi, Ohsumi, Keita, Gurdon, John B.
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Molecular Cell
ISSN: 1097-4164
1097-2765
Popis: Summary 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.
Graphical Abstract
Highlights • Xenopus oocytes induce an oocyte transcription pattern in mouse nuclei in 2 days • Reprogramming requires a switch from somatic to oocyte transcriptional components • Unusually high amounts of oocyte-derived RNA polymerase II drive reprogramming • The pattern of oocyte linker histone binding to somatic chromatin is revealed
Jullien et al. identify a sequence of events leading to rapid transcriptional reprogramming of somatic nuclei after their transplantation to Xenopus oocytes. Transcription is switched selectively to an oocyte-type program in a process involving stepwise loading of oocyte-specific factors onto transplanted chromatin.
Databáze: OpenAIRE
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