期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 107, 期 7, 页码 823-834出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI11385
关键词
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资金
- NHLBI NIH HHS [P01 HL019242, R01 HL038854, R01 HL-57353, R01 HL-38854, R01 HL057353, P01 HL-19242] Funding Source: Medline
- NICHD NIH HHS [U54 HD-28934, U54 HD028934] Funding Source: Medline
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 reg ulate 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-MNC 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.
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