Nuclear translocation and carboxyl-terminal domain phosphorylation of RNA polymerase II delineate the two phases of zygotic gene activation in mammalian embryos.
In mammalian embryos, zygotic gene transcription initiates after a limited number of cell divisions through a two-step process termed the zygotic gene activation (ZGA). Here we report that RNA polymerase II undergoes major changes in mouse and rabbit preimplantation embryos during the ZGA. In transcriptionally inactive unfertilized oocytes, the RNA polymerase II largest subunit is predominantly hyperphosphorylated on its carboxy-terminal domain (CTD). The CTD is markedly dephosphorylated several hours after fertilization, before the onset of a period characterized by a weak transcriptional activity. The largest subunit of RNA polymerase II then lacks immunological and drug-sensitivity characteristics related to its phosphorylation by the TFIIH-associated kinase and gradually translocates into the nuclei independently of DNA replication 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 requirement for further development (respectively at the 2- and 8/16-cell stage). As these events occurred in the presence of actinomycin D, the nuclear translocation of RNA polymerase II and the phosphorylation of the CTD might be major determinants of ZGA.
Bellier
S
S
Génétique Moléculaire, URA 1302 CNRS, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Cedex 05, France.
Chastant
S
S
Adenot
P
P
Vincent
M
M
Renard
J P
JP
Bensaude
O
O
D000818:Animals; D001692:Biological Transport; D001755:Blastocyst / Q000201:enzymology / Q000378:metabolism*; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D012319:RNA Polymerase II / Q000302:isolation & purification / Q000378:metabolism*; D011817:Rabbits; D013045:Species Specificity; D015533:Transcriptional Activation; D015053:Zygote / Q000201:enzymology / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D003609:Dactinomycin; D004004:Dichlororibofuranosylbenzimidazole; D011494:Protein Kinases; C060137:carboxy-terminal domain kinase; D012319:RNA Polymerase II