Developmental pattern of expression and genomic organization of the calponin-h1 gene. A contractile smooth muscle cell marker.
Calponin-h1 is a 34-kDa myofibrillar thin filament, actin-binding protein that is expressed exclusively in smooth muscle cells (SMCs) in adult animals. To examine the molecular mechanisms that regulate SMC-specific gene expression, we have examined the temporal, spatial, and cell cycle-regulated patterns of expression of calponin-h1 gene expression and isolated and structurally characterized the murine calponin-h1 gene. Calponin-h1 mRNA is expressed exclusively in SMC-containing tissues in adult animals. During murine embryonic development, calponin-h1 gene expression is (i) detectable in E9.5 embryos in the dorsal aorta, cardiac outflow tract, and tubular heart, (ii) sequentially up-regulated in SMC-containing tissues, and (iii) down-regulated to non-detectable levels in the heart during late fetal development. In addition, the gene is expressed in resting rat aortic SMCs, but its expression is rapidly down-regulated when growth-arrested cells reenter phase G1 of the cell cycle and proliferate. Calponin-h1 is encoded by a 10.7-kilobase single copy gene composed of seven exons, which is part of a multigene family. Transient transfection analyses demonstrated that 1.5 kilobases of calponin-h1 5'-flanking sequence is sufficient to program high level transcription of a luciferase reporter gene in cultured primary rat aortic SMCs and the smooth muscle cell line, A7r5. Taken together, these data suggest that the calponin-h1 gene will serve as an excellent model system with which to examine the molecular mechanisms that regulate SMC lineage specification, differentiation, and phenotypic modulation.
Samaha
F F
FF
Department of Medicine, University of Chicago, Illinois 60637, USA.
Ip
H S
HS
Morrisey
E E
EE
Seltzer
J
J
Tang
Z
Z
Solway
J
J
Parmacek
M S
MS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D000096985:Calponins
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D008840:Microfilament Proteins; D000096985:Calponins