title: The CDK9/cyclin T1 subunits of P-TEFb in mouse oocytes and preimplantation embryos: a possible role in embryonic genome activation.
abstract: BACKGROUND
  Two stages of genome activation have been identified in the mouse embryo. Specifically, minor transcriptional activation is evident at the one-cell stage and a second major episode of activation occurs at the two-cell stage. Nuclear translocation of RNA polymerase II and phosphorylation of the C-terminal domain (CTD) of the largest enzyme subunit are major determinants of embryonic genome activation. P-TEFb, the Pol II CTD kinase, regulates transcriptional elongation via phosphorylation of the serine 2 residues of the CTD.
  
  
  RESULTS
  Here, we show that the CDK9 and cyclin T1 subunits of P-TEFb are present in mouse oocytes and preimplantation embryos. Both proteins translocate to pronuclei at the late one-cell stage and are predominantly localized in nuclei at the two-cell stage. We additionally examine the effects of the CDK9-specific inhibitor, flavopiridol, on mouse preimplantation development. Our data show that treatment with the drug results in mislocalization of CDK9, cyclin T1, and phosphorylated Pol II, as well as developmental arrest at the two-cell stage.
  
  
  CONCLUSIONS
  A change in CDK9 localization from the cytoplasm to the pronucleus occurs at the time of minor embryonic genome activation, and CDK9 accumulation at the two-cell stage is evident, concomitant with major transcriptional activation of the embryonic genome. Moreover, CDK9 inhibition triggers a developmental block at the two-cell stage. Our findings clearly indicate that CDK9 is essential for embryonic genome activation in the mouse.
authors.affiliation: Department of Animal Science & Biotechnology, Research Center for Transgenic Cloned Pigs, Chungnam National University, Daejeon, Korea.
authors.forename: Reza K
authors.initials: RK
authors.lastname: Oqani
authors.forename: Hong R
authors.initials: HR
authors.lastname: Kim
authors.forename: Yun F
authors.initials: YF
authors.lastname: Diao
authors.forename: Chang S
authors.initials: CS
authors.lastname: Park
authors.forename: Dong I
authors.initials: DI
authors.lastname: Jin
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D056906:Cyclin T / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D042863:Cyclin-Dependent Kinase 9 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D042925:Positive Transcriptional Elongation Factor B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D056906:Cyclin T; D005419:Flavonoids; D007527:Isoenzymes; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; C077990:alvocidib; D042925:Positive Transcriptional Elongation Factor B; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II