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Nucleic Acids Research, 1990, Vol. 18, No. 21 6239-6246
© 1990


MOLECULAR BIOLOGY

A highly conserved enhancer downstream of the human MLC1/3 locus is a target for multiple myogenic determination factors

Nadia Rosenthal, Erick B. Berglund, Bruce M. Wentworth, Maria Donoghue, Barbara Winter1, Eva Bober1, Thomas Braun1 and Hans-Henning Arnold1,*

Department of Biochemistry, Boston University School of Medicine Boston, MA 02118, USA 1Department of Toxicology, Medical School, University of Hamburg FRG

*To whom correspondence should be addressed

Received August 3, 1990. Revised October 1, 1990. Accepted October 1, 1990.

A potent muscle-specific enhancer element, originally described in the rat myosin light chain (MLC) 1/3 locus located downstream of the coding region, is found in an analogous position in the human MLC1/3 gene. When linked to a CAT reporter gene and transfected into muscle or non-muscle cells, the human MLC enhancer directs high levels of muscle-specific gene expression from homologous or heterologous promoters, irrespective of position or orientation relative to the CAT transcription unit. A significant degree of sequence homology (over 85%) in the 3'-f1anking regions of the two MLC genes is restricted to a 200 bp sequence which lies approximately 1.5 kb downstream of the polyadenylatlon site in both species. The human enhancer sequence includes binding sites for human myogenic determination factors containing a common basic helix-loop-helix motif, and it can be trans-activated to varying degrees in non-muscle cells by these factors. This study establishes the MLC enhancer as an evolutionarily conserved, integral component of the MLC1/3 locus which constitutes a novel target for the action of myogenic determination factors.


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