HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 46, 45770-45776, November 14, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/46/45770    most recent M306056200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by O'Toole, P. J. Articles by Norton, J. D. Search for Related Content PubMed PubMed Citation Articles by O'Toole, P. J. Articles by Norton, J. D. Social Bookmarking                      What's this?

Id Proteins Negatively Regulate Basic Helix-Loop-Helix Transcription Factor Function by Disrupting Subnuclear Compartmentalization^*

Peter J. O'Toole, Toshiaki Inoue¶||, Lindsay Emerson, Ian E. G. Morrison, Alan R. Mackie**, Richard J. Cherry, and John D. Norton

From the Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, United Kingdom and the ^**Food Research Institute, Norwich Research Park, Norwich NR4 7UA, United Kingdom

Id helix-loop-helix (HLH) proteins act as global regulators of metazoan cell fate, cell growth, and differentiation. They heterodimerize with and inhibit the DNA-binding function of members of the basic helix-loop-helix (bHLH) family of transcription factors. Using real time fluorescence microscopy techniques in single living cells, we show here that nuclear pools of chromatin-associated bHLH transcription factor are freely exchangeable and in constant flux. The existence of a dynamic equilibrium between DNA-bound and free bHLH protein is also directly demonstrable in vitro. By contrast, Id protein is not associated with any subcellular, macromolecular structures and displays a more highly mobile, diffuse nuclear-cytoplasmic distribution. When co-expressed with antagonist Id protein, the chromatin-associated sublocalization of bHLH protein is abolished, and there is an accompanying 100-fold increase in its nuclear mobility to a level expected for freely diffusible Id-bHLH heterodimer. These results suggest that nuclear Id protein acts by sequestering pools of transiently diffusing bHLH protein to prevent reassociation with chromatin domains. Such a mechanism would explain how Id proteins are able to overcome the large DNA-binding free energy of bHLH proteins that is necessary to accomplish their inhibitory effect.

Received for publication, June 9, 2003 , and in revised form, August 22, 2003.

^* This work was supported by the Wellcome Trust. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Dept. of Biology (Area 15), University of York, P. O. Box 373, York, YO10 5YW, United Kingdom.

^¶ Present address: Dept. of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1, Seiryo-machi, Aobu-ku, Sendai, 980-8575, Japan.

^|| Supported in part by a Yamada Science Foundation Fellowship.

To whom correspondence should be addressed: Dept. of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, United Kingdom. Tel.: 44-1206-872918; Fax: 44-1206-872592; E-mail: jnorton{at}essex.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Kaneko, X. Li, X. Zhang, J. J. Lamberti, S. W. Jamieson, and P. A. Thistlethwaite Endothelial Expression of Bone Morphogenetic Protein Receptor Type 1a is Required for Atrioventricular Valve Formation. Ann. Thorac. Surg., June 1, 2008; 85(6): 2090 - 2098. [Abstract] [Full Text] [PDF]

				M. Carroll, M. Hamzeh, and B. Robaire Expression, Localization, and Regulation of Inhibitor of DNA Binding (Id) Proteins in the Rat Epididymis J Androl, March 1, 2006; 27(2): 212 - 224. [Abstract] [Full Text] [PDF]

				H. Kurooka and Y. Yokota Nucleo-cytoplasmic Shuttling of Id2, a Negative Regulator of Basic Helix-Loop-Helix Transcription Factors J. Biol. Chem., February 11, 2005; 280(6): 4313 - 4320. [Abstract] [Full Text] [PDF]

				T. Lofstedt, A. Jogi, M. Sigvardsson, K. Gradin, L. Poellinger, S. Pahlman, and H. Axelson Induction of ID2 Expression by Hypoxia-inducible Factor-1: A ROLE IN DEDIFFERENTIATION OF HYPOXIC NEUROBLASTOMA CELLS J. Biol. Chem., September 17, 2004; 279(38): 39223 - 39231. [Abstract] [Full Text] [PDF]