CArG elements control smooth muscle subtype–specific expression of smooth muscle myosin in vivo
AUTOR(ES)
Manabe, Ichiro
FONTE
American Society for Clinical Investigation
RESUMO
Expression of smooth muscle myosin heavy chain (SM-MHC) is tightly controlled depending on the differentiated state of smooth muscle cells (SMCs). To better understand the mechanisms that regulate transcription of the SM-MHC gene in vivo, we tested the function of several conserved CArG elements contained within the –4200 to +11600 region of this gene that we had previously shown to drive SMC-specific expression in transgenic mice. CArG1 in the 5′-flanking sequence was required for all SMCs, while CArG2 and a novel intronic CArG element were differentially required in SMC subtypes. Of particular note, mutation of the intronic CArG selectively abolished expression in large arteries. A promoter construct containing three repeats of a conserved 227-bp intronic CArG-containing region was sufficient to direct transcription in vascular SMCs in transgenic mice, although this construct was also expressed in skeletal and cardiac muscle. These results support a model in which transcriptional regulation of SM-MHC is controlled by multiple positive and negative modular control regions that differ between SMCs and non-SMCs and among SMC subtypes. We also demonstrated that the CArG elements of the endogenous SM-MHC gene were bound by SRF in chromatin.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=199571Documentos Relacionados
- 5′ CArG degeneracy in smooth muscle α-actin is required for injury-induced gene suppression in vivo
- Electrical synapses in retinal ON cone bipolar cells: Subtype-specific expression of connexins
- Cyanotriphenylborate: subtype-specific blocker of glycine receptor chloride channels.
- Myocardin-dependent Activation of the CArG Box-rich Smooth Muscle γ-Actin Gene: PREFERENTIAL UTILIZATION OF A SINGLE CArG ELEMENT THROUGH FUNCTIONAL ASSOCIATION WITH THE NKX3.1 HOMEODOMAIN PROTEIN*
- Natural and synthetic DNA elements with the CArG motif differ in expression and protein-binding properties.