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Mol Cell August 21, 2014; 55 (4): 524-36.

Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming.

Jullien J , Miyamoto K , Pasque V , Allen GE , Bradshaw CR , Garrett NJ , Halley-Stott RP , Kimura H , Ohsumi K , Gurdon JB .

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.

PubMed ID: 25066233
PMC ID: PMC4156308
Article link: Mol Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: h2bc21 lefty myc pou5f3.1 rbp1 sox2 tbp tbpl2

Article Images: [+] show captions
References [+] :
Akhtar, TBP2 is a substitute for TBP in Xenopus oocyte transcription. 2009, Pubmed, Xenbase