title: Human SM22 alpha BAC encompasses regulatory sequences for expression in vascular and visceral smooth muscles at fetal and adult stages.
abstract: The SM22 alpha gene has widely been used to study the regulatory mechanisms of smooth muscle cell (SMC) gene expression during cardiovascular development. To determine the regulatory mechanisms for the evolutionarily conserved human SM22 alpha (hSM22 alpha) gene, we demonstrated that 445 bp upstream DNA sequences of hSM22 alpha gene exhibited a high transcriptional activity in arterial SMC, not in venous nor in visceral SMCs during embryogensis. However, this promoter was gradually turned off in adulthood. Inclusion of the first intron in this promoter suppressed the promoter activity in pulmonary trunk arterial SMCs, whereas the expression in other systemic vasculature remained similar to that of the hSM22-445 promoter during the fetal and adult stages. To determine whether additional sequences are required for SM22 alpha expression in all subtypes of SMCs, we examined the expression of a bacterial artificial chromosome containing the hSM22 alpha locus in transgenic mice. The hSM22 alpha transgene showed similar developmental expression patterns as the endogenous mouse SM22 alpha gene, suggesting that this bacterial artificial chromosome contains essential regulatory sequences for its expression in arterial, venous, and visceral tissues during development.
authors.affiliation: Department of Internal Medicine, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Ye-Shih
authors.initials: YS
authors.lastname: Ho
authors.forename: Raquel P
authors.initials: RP
authors.lastname: Ritchie
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics*; D004064:Digestive System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D009130:Muscle, Smooth / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D014162:Transfection; D014781:Viscera; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; C058992:Tagln protein, mouse; C051615:transgelin; D001616:beta-Galactosidase