Cell cycle gene-specific control of transcription has a critical role in proliferation of primordial germ cells
- Daiji Okamura1,2,
- Ikuma Maeda1,
- Hirofumi Taniguchi1,
- Yuko Tokitake1,
- Makiko Ikeda1,
- Keiko Ozato3,
- Nathan Mise4,7,
- Kuniya Abe4,
- Toshiaki Noce5,
- Juan Carlos Izpisua Belmonte2,6,8 and
- Yasuhisa Matsui1,8
- 1Cell Resource Center for Biomedical Research, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan;
- 2Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA;
- 3Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892, USA;
- 4Mammalian Cellular Dynamics, RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan;
- 5Department of Physiology, School of Medicine, Keio University, Tokyo 113-0021, Japan;
- 6Center of Regenerative Medicine in Barcelona, Barcelona 08003, Spain
Abstract
Transcription elongation is stimulated by positive transcription elongation factor b (P-TEFb), for which activity is repressed in the 7SK small nuclear ribonucleoprotein (7SK snRNP) complex. We show here a critical role of 7SK snRNP in growth control of primordial germ cells (PGCs). The expression of p15INK4b, a cyclin-dependent kinase inhibitor (CDKI) gene, in PGCs is selectively activated by P-TEFb and its recruiting molecule, Brd4, when the amount of active P-TEFb is increased due to reduction of the 7SK snRNP, and PGCs consequently undergo growth arrest. These results indicate that CDKI gene-specific control of transcription by 7SK snRNP plays a pivotal role in the maintenance of PGC proliferation.
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Footnotes
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↵8 Corresponding authors
E-mail belmonte{at}salk.edu
E-mail ymatsui{at}idac.tohoku.ac.jp
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.202242.112.
- Received July 26, 2012.
- Accepted September 26, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press