A highly conserved enhancer downstream of the human MLC1/3 locus is a target for multiple myogenic determination factors.
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'-flanking regions of the two MLC genes is restricted to a 200 bp sequence which lies approximately 1.5 kb downstream of the polyadenylation 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.
Rosenthal
N
N
Department of Biochemistry, Boston University School of Medicine, MA 02118.
Berglund
E B
EB
Wentworth
B M
BM
Donoghue
M
M
Winter
B
B
Bober
E
E
Braun
T
T
Arnold
H H
HH
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D005796:Genes; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009218:Myosins / Q000235:genetics*; D010957:Plasmids; D051381:Rats; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D009218:Myosins