Modular elements of the MLC 1f/3f locus confer fiber-specific transcription regulation in transgenic mice.
The two proteins encoded by the fast alkali myosin light chain (MLC) 1f/3f locus are developmentally regulated, muscle specific, and expressed exclusively in fast-twitch fibers. Their expression is independently regulated by two separate promoters and a downstream enhancer. Previous studies showed a reporter gene directed by the rat MLC If promoter and MLC enhancer to exhibit correct skeletal muscle-specific expression in transgenic mice during development and to be preferentially expressed in fast-twitch Type IIB fibers [Donoghue et al., (1991) J. Cell B.ol. 115:423-434]. The MLC 3f promoter also directed muscle-specific expression of a CAT reporter gene in adult transgenic mice and showed little dependence upon the enhancer. Here, we show that the MLC 3f promoter also directs transgene expression in the fast-twitch fibers of adult skeletal muscle, but almost exclusively to fiber Types IIA and IIX. MLC 3f transgene expression occurs in only a subset of the fiber types that express the endogenous locus, indicating modular elements included in the transgene confer fiber-specific transcription regulation. MyoD protein was also found to be restricted to fiber Types IIA and IIX, providing evidence for its possible role in mediating fiber-specific gene expression.
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown 02129-2060, USA.
C
C
Neville
D
D
Gonzales
L
L
Houghton
M J
MJ
McGrew
N
N
Rosenthal
D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development; D018656:Muscle Fibers, Fast-Twitch / Q000145:classification / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development*; D017570:MyoD Protein / Q000096:biosynthesis / Q000235:genetics; D018994:Myosin Light Chains / Q000235:genetics*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000235:genetics*; D019076:Transgenes
D009124:Muscle Proteins; D017570:MyoD Protein; D018994:Myosin Light Chains; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase