• This record comes from PubMed

Cyclin T2 is essential for mouse embryogenesis

. 2009 Jun ; 29 (12) : 3280-5. [epub] 20090413

Language English Country United States Media print-electronic

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Grant support
P50 GM082250 NIGMS NIH HHS - United States

The positive transcription elongation factor b (P-TEFb) is essential for the elongation of transcription and cotranscriptional processing by RNA polymerase II. In mammals, it contains predominantly the C-type cyclin cyclin T1 (CycT1) or CycT2 and cyclin-dependent kinase 9 (Cdk9). To determine if these cyclins have redundant functions or affect distinct sets of genes, we genetically inactivated the CycT2 gene (Ccnt2) using the beta-galactosidase-neomycin gene (beta-geo) gene trap technology in the mouse. Visualizing beta-galactosidase during mouse embryogenesis revealed that CycT2 is expressed abundantly during embryogenesis and throughout the organism in the adult. This finding was reflected in the expression of CycT2 in all adult tissues and organs. However, despite numerous matings of heterozygous mice, we observed no CycT2(-/-) embryos, pups, or adult mice. This early lethality could have resulted from decreased expression of critical genes, which were revealed by short interfering RNAs against CycT2 in embryonic stem cells. Thus, CycT1 and CycT2 are not redundant, and these different P-TEFb complexes regulate subsets of distinct genes that are important for embryonic development.

See more in PubMed

Adjaye, J., J. Huntriss, R. Herwig, A. BenKahla, T. C. Brink, C. Wierling, C. Hultschig, D. Groth, M. L. Yaspo, H. M. Picton, R. G. Gosden, and H. Lehrach. 2005. Primary differentiation in the human blastocyst: comparative molecular portraits of inner cell mass and trophectoderm cells. Stem Cells 231514-1525. PubMed

Bagella, L., T. K. MacLachlan, R. J. Buono, M. M. Pisano, A. Giordano, and A. De Luca. 1998. Cloning of murine CDK9/PITALRE and its tissue-specific expression in development. J. Cell Physiol. 177206-213. PubMed

Barboric, M., R. M. Nissen, S. Kanazawa, N. Jabrane-Ferrat, and B. M. Peterlin. 2001. NF-κB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol. Cell 8327-337. PubMed

Bellier, S., S. Chastant, P. Adenot, M. Vincent, J. P. Renard, and O. Bensaude. 1997. Nuclear translocation and carboxyl-terminal domain phosphorylation of RNA polymerase II delineate the two phases of zygotic gene activation in mammalian embryos. EMBO J. 166250-6262. PubMed PMC

Besser, D. 2004. Expression of nodal, lefty-A, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3. J. Biol. Chem. 27945076-45084. PubMed

Brasier, A. R. 2008. Expanding role of cyclin dependent kinases in cytokine inducible gene expression. Cell Cycle 72661-2666. PubMed PMC

Chao, S. H., and D. H. Price. 2001. Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo. J. Biol. Chem. 27631793-31799. PubMed

Cujec, T. P., H. Okamoto, K. Fujinaga, J. Meyer, H. Chamberlin, D. O. Morgan, and B. M. Peterlin. 1997. The HIV transactivator TAT binds to the CDK-activating kinase and activates the phosphorylation of the carboxy-terminal domain of RNA polymerase II. Genes Dev. 112645-2657. PubMed PMC

Doty, R. T., G. J. Vanasse, C. M. Disteche, and D. M. Willerford. 2002. The leukemia-associated gene Mllt1/ENL: characterization of a murine homolog and demonstration of an essential role in embryonic development. Blood Cells Mol. Dis. 28407-417. PubMed

Elagib, K. E., I. S. Mihaylov, L. L. Delehanty, G. C. Bullock, K. D. Ouma, J. F. Caronia, S. L. Gonias, and A. N. Goldfarb. 2008. Cross-talk of GATA-1 and P-TEFb in megakaryocyte differentiation. Blood 1124884-4894. PubMed PMC

Evsikov, A. V., J. H. Graber, J. M. Brockman, A. Hampl, A. E. Holbrook, P. Singh, J. J. Eppig, D. Solter, and B. B. Knowles. 2006. Cracking the egg: molecular dynamics and evolutionary aspects of the transition from the fully grown oocyte to embryo. Genes Dev. 202713-2727. PubMed PMC

Gosden, R. G. 2002. Oogenesis as a foundation for embryogenesis. Mol. Cell Endocrinol. 186149-153. PubMed

Jiang, H., and B. M. Peterlin. 2008. Differential chromatin looping regulates CD4 expression in immature thymocytes. Mol. Cell. Biol. 28907-912. PubMed PMC

Kanazawa, S., T. Okamoto, and B. M. Peterlin. 2000. Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection. Immunity 1261-70. PubMed

Kanazawa, S., L. Soucek, G. Evan, T. Okamoto, and B. M. Peterlin. 2003. c-Myc recruits P-TEFb for transcription, cellular proliferation and apoptosis. Oncogene 225707-5711. PubMed

Kohoutek, J., D. Blazek, and B. M. Peterlin. 2006. Hexim1 sequesters positive transcription elongation factor b from the class II transactivator on MHC class II promoters. Proc. Natl. Acad. Sci. USA 10317349-17354. PubMed PMC

Kurosu, T., F. Zhang, and B. M. Peterlin. 2004. Transcriptional activity and substrate recognition of cyclin T2 from P-TEFb. Gene 343173-179. PubMed

Lin, X., R. Taube, K. Fujinaga, and B. M. Peterlin. 2002. P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA. J. Biol. Chem. 27716873-16878. PubMed

Margaritis, T., and F. C. Holstege. 2008. Poised RNA polymerase II gives pause for thought. Cell 133581-584. PubMed

Marshall, R. M., D. Salerno, J. Garriga, and X. Grana. 2005. Cyclin T1 expression is regulated by multiple signaling pathways and mechanisms during activation of human peripheral blood lymphocytes. J. Immunol. 1756402-6411. PubMed

Meno, C., K. Gritsman, S. Ohishi, Y. Ohfuji, E. Heckscher, K. Mochida, A. Shimono, H. Kondoh, W. S. Talbot, E. J. Robertson, A. F. Schier, and H. Hamada. 1999. Mouse Lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation. Mol. Cell 4287-298. PubMed

Meno, C., A. Shimono, Y. Saijoh, K. Yashiro, K. Mochida, S. Ohishi, S. Noji, H. Kondoh, and H. Hamada. 1998. lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal. Cell 94287-297. PubMed

Mueller, D., C. Bach, D. Zeisig, M. P. Garcia-Cuellar, S. Monroe, A. Sreekumar, R. Zhou, A. Nesvizhskii, A. Chinnaiyan, J. L. Hess, and R. K. Slany. 2007. A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 1104445-4454. PubMed PMC

Oven, I., N. Brdickova, J. Kohoutek, T. Vaupotic, M. Narat, and B. M. Peterlin. 2007. AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells. Mol. Cell. Biol. 278815-8823. PubMed PMC

Peterlin, B. M., and D. H. Price. 2006. Controlling the elongation phase of transcription with P-TEFb. Mol. Cell 23297-305. PubMed

Pratt, H. P., V. N. Bolton, and K. A. Gudgeon. 1983. The legacy from the oocyte and its role in controlling early development of the mouse embryo. Ciba Found Symp. 98197-227. PubMed

Saunders, A., L. J. Core, and J. T. Lis. 2006. Breaking barriers to transcription elongation. Nat. Rev. Mol. Cell Biol. 7557-567. PubMed

Shim, E. Y., A. K. Walker, Y. Shi, and T. K. Blackwell. 2002. CDK-9/cyclin T (P-TEFb) is required in two postinitiation pathways for transcription in the C. elegans embryo. Genes Dev. 162135-2146. PubMed PMC

Shimizu, N., R. Ouchida, N. Yoshikawa, T. Hisada, H. Watanabe, K. Okamoto, M. Kusuhara, H. Handa, C. Morimoto, and H. Tanaka. 2005. HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b. Proc. Natl. Acad. Sci. USA 1028555-8560. PubMed PMC

Schnutgen, F., S. De-Zolt, P. Van Sloun, M. Hollatz, T. Floss, J. Hansen, J. Altschmied, C. Seisenberger, N. B. Ghyselinck, P. Ruiz, P. Chambon, W. Wurst, and H. von Melchner. 2005. Genomewide production of multipurpose alleles for the functional analysis of the mouse genome. Proc. Natl. Acad. Sci. USA 1027221-7226. PubMed PMC

Simone, C., L. Bagella, C. Bellan, and A. Giordano. 2002. Physical interaction between pRb and cdk9/cyclinT2 complex. Oncogene 214158-4165. PubMed

Simone, C., P. Stiegler, L. Bagella, B. Pucci, C. Bellan, G. De Falco, A. De Luca, G. Guanti, P. L. Puri, and A. Giordano. 2002. Activation of MyoD-dependent transcription by cdk9/cyclin T2. Oncogene 214137-4148. PubMed

Taube, R., X. Lin, D. Irwin, K. Fujinaga, and B. M. Peterlin. 2002. Interaction between P-TEFb and the C-terminal domain of RNA polymerase II activates transcriptional elongation from sites upstream or downstream of target genes. Mol. Cell. Biol. 22321-331. PubMed PMC

Tsukamoto, S., A. Kuma, M. Murakami, C. Kishi, A. Yamamoto, and N. Mizushima. 2008. Autophagy is essential for preimplantation development of mouse embryos. Science 321117-120. PubMed

Wimmer, J., K. Fujinaga, R. Taube, T. P. Cujec, Y. Zhu, J. Peng, D. H. Price, and B. M. Peterlin. 1999. Interactions between Tat and TAR and human immunodeficiency virus replication are facilitated by human cyclin T1 but not cyclins T2a or T2b. Virology 255182-189. PubMed

Wittmann, B. M., N. Wang, and M. M. Montano. 2003. Identification of a novel inhibitor of breast cell growth that is down-regulated by estrogens and decreased in breast tumors. Cancer Res. 635151-5158. PubMed

Yu, W., R. Ramakrishnan, Y. Wang, K. Chiang, T. L. Sung, and A. P. Rice. 2008. Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors. PLoS ONE 3e3146. PubMed PMC

Yu, W., Y. Wang, C. A. Shaw, X. F. Qin, and A. P. Rice. 2006. Induction of the HIV-1 Tat co-factor cyclin T1 during monocyte differentiation is required for the regulated expression of a large portion of cellular mRNAs. Retrovirology 332. PubMed PMC

Newest 20 citations...

See more in
Medvik | PubMed

Perspective of cyclin-dependent kinase 9 (CDK9) as a drug target

. 2012 ; 18 (20) : 2883-90.

Cyclin K goes with Cdk12 and Cdk13

. 2012 Apr 18 ; 7 () : 12. [epub] 20120418

P-TEFb- the final frontier

. 2009 Sep 02 ; 4 () : 19. [epub] 20090902

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...