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.
Department of Medicine, University of Chicago, Illinois 60637, USA.
F F
FF
Samaha
H S
HS
Ip
E E
EE
Morrisey
J
J
Seltzer
Z
Z
Tang
J
J
Solway
M S
MS
Parmacek
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