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DNA Binding and Transcriptional Regulatory Activity of Mammalian Achaete-Acute Homologous (MASH) Proteins Revealed by Interaction with a Muscle-Specific Enhancer

Johnson, Jane E. and Birren, Susan J. and Saito, Tetsuichiro and Anderson, David J. (1992) DNA Binding and Transcriptional Regulatory Activity of Mammalian Achaete-Acute Homologous (MASH) Proteins Revealed by Interaction with a Muscle-Specific Enhancer. Proceedings of the National Academy of Sciences of the United States of America, 89 (8). pp. 3596-3600. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:JOHpnas92

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Abstract

The MASH genes are vertebrate homologues of achaete-scute, genes required for neuronal determination in Drosophila. The sequence of MASH1 and MASH2 contains a basic helix-loop-helix (bHLH) motif that is present in other transcriptional regulators such as MyoD and E12. In the absence of an authentic target for the MASH proteins, we examined their DNA binding and transcriptional regulatory activity by using a binding site (the E box) from the muscle creatine kinase (MCK) gene, a target of MyoD. Like myogenic bHLH proteins, the MASH proteins form heterooligomers with E12 that bind the MCK E box with high affinity in vitro. Unexpectedly, however, MASH1 and MASH2 also activate transcription of both exogenous and endogenous MCK in transfected C3H/10T1/2 fibroblasts. However, they do not induce myogenesis. Myogenic activity is not exclusively a property of the MyoD basic region, as substitution of this domain fails to confer myogenic activity on MASH1. These data suggest that different bHLH proteins may activate overlapping but distinct sets of target genes in the same cell type.


Item Type:Article
Additional Information:Copyright © 1992 by National Academy of Sciences Communicated by Melvin I. Simon, January 2, 1992 (received for review October 9, 1991) S.J.B. and T.S. contributed equally to this work. We thank Dr. J. Buskin, Dr. M. Weber, Mr. J. Montgomery, Dr. J. Miner, Dr. R. Benezra, and Dr. H. Weintraub for providing plasmids; Dr. S. Hauschka for providing the MCK and MF20 antibodies; Mr. S. Padilla for excellent technical assistance; and Ms. Helen Walsh for manuscript preparation. We thank Drs. B. Wold and T. Wilkie for their critical reading of the manuscript. J.E.J. was supported by a Muscular Dystrophy Association postdoctoral fellowship, and S.J.B. was supported by a Pew Faculty Fellowship in the Neurosciences. T.S. is an Associate and D.J.A. is an Assistant Investigator of the Howard Hughes Medical Institute. This work was supported in part by a Sloan Foundation Fellowship in Neuroscience and a National Science Foundation Presidential Young Investigator Award to D.J.A. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:basic helix-loop-helix proteins; MyoD; achaete-scute homologues; determination genes
Record Number:CaltechAUTHORS:JOHpnas92
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:JOHpnas92
Alternative URL:http://www.pnas.org/cgi/content/abstract/89/8/3596
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6396
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:07 Dec 2006
Last Modified:26 Dec 2012 09:20

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