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

Journal: 
Mol Cell
Publication Year: 
2014
Authors: 
Jerome Jullien
Kei Miyamoto
Vincent Pasque
George E Allen
Charles R Bradshaw
Nigel J Garrett
Richard P Halley-Stott
Hiroshi Kimura
Keita Ohsumi
John B Gurdon
PubMed link: 
25066233
Public Summary: 
In this work we identified how key molecules stored in an oocyte reprogram somatic nuclei following nuclear transfer.
Scientific 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.