Previous Article | Next Article 
Mol Cell Biol, March 1998, p. 1467-1476, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Repression of TFIIH Transcriptional Activity
and TFIIH-Associated cdk7 Kinase Activity at Mitosis
John J.
Long,
Anne
Leresche,
Richard W.
Kriwacki,
and
Joel M.
Gottesfeld*
Department of Molecular Biology, The Scripps
Research Institute, La Jolla, California 92037
Received 4 August 1997/Returned for modification 3 October
1997/Accepted 15 December 1997
Nuclear transcription is repressed when eukaryotic cells enter
mitosis. Mitotic repression of transcription of various cellular and
viral gene promoters by RNA polymerase II can be reproduced in vitro
either with extracts prepared from cells arrested at mitosis with the
microtubule polymerization inhibitor nocodazole or with nuclear
extracts prepared from asynchronous cells and the mitotic protein
kinase cdc2/cyclin B. Purified cdc2/cyclin B kinase is also sufficient
to inhibit transcription in reconstituted transcription reactions with
biochemically purified and recombinant basal transcription factors and
RNA polymerase II. The cyclin-dependent kinase inhibitor
p21Waf1/Cip1/Sdi1 can reverse the effect of
cdc2/cyclin B kinase, indicating that repression of transcription is
due to protein phosphorylation. Transcription rescue and inhibition
experiments with each of the basal factors and the polymerase suggest
that multiple components of the transcription machinery are inactivated
by cdc2/cyclin B kinase. For an activated promoter, targets of
repression are TFIID and TFIIH, while for a basal promoter, TFIIH is
the major target for mitotic inactivation of transcription. Protein
labeling experiments indicate that the p62 and p36 subunits of TFIIH
are in vitro substrates for mitotic phosphorylation. Using the
carboxy-terminal domain of the large subunit of RNA polymerase II as a
test substrate for phosphorylation, the TFIIH-associated kinase,
cdk7/cyclin H, is inhibited concomitant with inhibition of
transcription activity. Our results suggest that there exist multiple
phosphorylation targets for the global shutdown of transcription at
mitosis.
*
Corresponding author. Mailing address: Department of
Molecular Biology, The Scripps Research Institute, 10550 N. Torrey
Pines Rd., La Jolla, CA 92037. Phone: (619) 784-8913. Fax: (619)
784-8965. E-mail: joelg{at}scripps.edu.

Present address: Baxter Pharmaceuticals, Neuchatel, Switzerland.

Present address: Department of Structural Biology, St. Jude
Children's Research Hospital, Memphis, TN 38105.
This article has been cited by other articles:
-
Boeing, S., Rigault, C., Heidemann, M., Eick, D., Meisterernst, M.
(2010). RNA Polymerase II C-terminal Heptarepeat Domain Ser-7 Phosphorylation Is Established in a Mediator-dependent Fashion. J. Biol. Chem.
285: 188-196
[Abstract]
[Full Text]
-
Xu, Y.-X., Manley, J. L.
(2007). Pin1 modulates RNA polymerase II activity during the transcription cycle. Genes Dev.
21: 2950-2962
[Abstract]
[Full Text]
-
Aguilar-Fuentes, J., Valadez-Graham, V., Reynaud, E., Zurita, M.
(2006). TFIIH trafficking and its nuclear assembly during early Drosophila embryo development. J. Cell Sci.
119: 3866-3875
[Abstract]
[Full Text]
-
Souid, A.-K., Gao, C., Wang, L., Milgrom, E., Shen, W.-C. W.
(2006). ELM1 Is Required for Multidrug Resistance in Saccharomyces cerevisiae. Genetics
173: 1919-1937
[Abstract]
[Full Text]
-
Staudt, N., Fellert, S., Chung, H.-R., Jackle, H., Vorbruggen, G.
(2006). Mutations of the Drosophila Zinc Finger-encoding Gene vielfaltig Impair Mitotic Cell Divisions and Cause Improper Chromosome Segregation. Mol. Biol. Cell
17: 2356-2365
[Abstract]
[Full Text]
-
Fisher, R. P.
(2005). Secrets of a double agent: CDK7 in cell-cycle control and transcription. J. Cell Sci.
118: 5171-5180
[Abstract]
[Full Text]
-
Jantz, D., Berg, J. M.
(2004). Reduction in DNA-binding affinity of Cys2His2 zinc finger proteins by linker phosphorylation. Proc. Natl. Acad. Sci. USA
101: 7589-7593
[Abstract]
[Full Text]
-
Xu, Y.-X., Hirose, Y., Zhou, X. Z., Lu, K. P., Manley, J. L.
(2003). Pin1 modulates the structure and function of human RNA polymerase II. Genes Dev.
17: 2765-2776
[Abstract]
[Full Text]
-
Dovat, S., Ronni, T., Russell, D., Ferrini, R., Cobb, B. S., Smale, S. T.
(2002). A common mechanism for mitotic inactivation of C2H2 zinc finger DNA-binding domains. Genes Dev.
16: 2985-2990
[Abstract]
[Full Text]
-
Ehley, J. A., Melander, C., Herman, D., Baird, E. E., Ferguson, H. A., Goodrich, J. A., Dervan, P. B., Gottesfeld, J. M.
(2002). Promoter Scanning for Transcription Inhibition with DNA-Binding Polyamides. Mol. Cell. Biol.
22: 1723-1733
[Abstract]
[Full Text]
-
Matt Kim, J., McGaughy, J. T., Kent Bogle, R., Ravnik, S. E.
(2001). Meiotic Expression of the Cyclin H/Cdk7 Complex in Male Germ Cells of the Mouse. Biol. Reprod.
64: 1400-1408
[Abstract]
[Full Text]
-
Nissen, R. M., Yamamoto, K. R.
(2000). The glucocorticoid receptor inhibits NFkappa B by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev.
14: 2314-2329
[Abstract]
[Full Text]
-
Spencer, C. A., Kruhlak, M. J., Jenkins, H. L., Sun, X., Bazett-Jones, D. P.
(2000). Mitotic Transcription Repression in Vivo in the Absence of Nucleosomal Chromatin Condensation. JCB
150: 13-26
[Abstract]
[Full Text]
-
Castaño, E., Gross, P., Wang, Z., Roeder, R. G., Oelgeschläger, T.
(2000). The C-terminal domain-phosphorylated IIO form of RNA polymerase II is associated with the transcription repressor NC2 (Dr1/DRAP1) and is required for transcription activation in human nuclear extracts. Proc. Natl. Acad. Sci. USA
10.1073/pnas.140202297v1
[Abstract]
[Full Text]
-
Sirri, V., Roussel, P., Hernandez-Verdun, D.
(2000). In Vivo Release of Mitotic Silencing of Ribosomal Gene Transcription Does Not Give Rise to Precursor Ribosomal RNA Processing. JCB
148: 259-270
[Abstract]
[Full Text]
-
Kimmelman, J., Kaldis, P., Hengartner, C. J., Laff, G. M., Koh, S. S., Young, R. A., Solomon, M. J.
(1999). Activating Phosphorylation of the Kin28p Subunit of Yeast TFIIH by Cak1p. Mol. Cell. Biol.
19: 4774-4787
[Abstract]
[Full Text]
-
Klein, J., Grummt, I.
(1999). Cell cycle-dependent regulation of RNA polymerase I transcription: The nucleolar transcription factor UBF is inactive in mitosis and early G1. Proc. Natl. Acad. Sci. USA
96: 6096-6101
[Abstract]
[Full Text]
-
Melnick, A., Licht, J. D.
(1999). Deconstructing a Disease: RAR{alpha}, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia. Blood
93: 3167-3215
[Full Text]
-
Reynaud, E., Lomelí, H., Vázquez, M., Zurita, M.
(1999). The Drosophila melanogaster Homologue of the Xeroderma Pigmentosum D Gene Product Is Located in Euchromatic Regions and Has a Dynamic Response to UV Light-induced Lesions in Polytene Chromosomes. Mol. Biol. Cell
10: 1191-1203
[Abstract]
[Full Text]
-
Akoulitchev, S., Reinberg, D.
(1998). The molecular mechanism of mitotic inhibition of TFIIH is mediated by phosphorylation of CDK7. Genes Dev.
12: 3541-3550
[Abstract]
[Full Text]
-
Dickinson, L. A., Gulizia, R. J., Trauger, J. W., Baird, E. E., Mosier, D. E., Gottesfeld, J. M., Dervan, P. B.
(1998). Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands. Proc. Natl. Acad. Sci. USA
95: 12890-12895
[Abstract]
[Full Text]
-
Zhou, M., Nekhai, S., Bharucha, D. C., Kumar, A., Ge, H., Price, D. H., Egly, J.-M., Brady, J. N.
(2001). TFIIH Inhibits CDK9 Phosphorylation during Human Immunodeficiency Virus Type 1 Transcription. J. Biol. Chem.
276: 44633-44640
[Abstract]
[Full Text]
-
Castano, E., Gross, P., Wang, Z., Roeder, R. G., Oelgeschlager, T.
(2000). The C-terminal domain-phosphorylated IIO form of RNA polymerase II is associated with the transcription repressor NC2 (Dr1/DRAP1) and is required for transcription activation in human nuclear extracts. Proc. Natl. Acad. Sci. USA
97: 7184-7189
[Abstract]
[Full Text]