NUCLEAR TRANSLOCATION AND CARBOXYL-TERMINAL DOMAIN PHOSPHORYLATION OFRNA-POLYMERASE-II DELINEATE THE 2 PHASES OF ZYGOTIC GENE ACTIVATION IN MAMMALIAN EMBRYOS

In mammalian embryos, zygotic gene transcription initiates after a lim ited number of cell divisions through a two-step process termed the zy gotic gene activation (ZGA), Here we report that RNA polymerase IT und ergoes major changes in mouse and rabbit preimplantation embryos durin g the ZGA, Tn transcriptionally inactive unfertilized oocytes, the RNA polymerase II largest subunit is predominantly hyperphosphorylated on its carboxy-terminal domain (CTD), The CTD is markedly dephosphorylat ed several hours after fertilization, before the onset of a period cha racterized by a weak transcriptional activity. The largest subunit of RNA polymerase II then lacks immunological and drug-sensitivity charac teristics related to its phosphorylation by the TFIIH-associated kinas e and gradually translocates into the nuclei independently of DNA repl ication and mitosis, A phosphorylation pattern of the largest subunit, close to that observed in somatic cells, is established in both mouse and rabbit embryos at the stage when transcription becomes a requirem ent for further development (respectively at the 2- and 8/16-cell stag e), As these events occurred in the presence of actinomycin D, the nuc lear translocation of RNA polymerase II and the phosphorylation of the CTD might be major determinants of ZGA.