Regulation of type I collagen genes expression.
Type I collagen, the most abundant protein of the body, is preferentially synthesized in bone, dermis, and tendons by two cell types, the osteoblast and the fibroblast. The expression of type I collagen is increased in the various forms of fibrosis such as lung, liver, bone marrow fibrosis and scleroderma. Type I collagen is a heterotrimer molecule consisting of two alpha 1(I) chains and one alpha 2(I) chain. The two polypeptide chains are synthesized in a 2:1 stoichiometry. The same 2:1 ratio is observed for the rate of synthesis of the corresponding mRNAs. One hypothesis that would explain how this coregulation occurs at the transcriptional level is that common cis-acting elements are present on both genes. These common regulatory elements would bind identical transcription factors displaying the same function. The characterization of the various regulatory elements present in these genes would foster our understanding of the molecular mechanisms controlling type I collagen gene expression in normal and in pathological situations. Over the past few years, several laboratories have identified cis-acting elements in the promoters of the COL1A1 and COL1A2 genes. At least, two of these cis-acting elements are common to both promoters. One is centered by a pentanucleotide CCAAT and binds a ubiquitously expressed heteromeric CCAAT binding factor. A second one is centered by a G-rich region and it binds a new transcription factor called C-Krox.(ABSTRACT TRUNCATED AT 250 WORDS)
Karsenty
G
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University of Texas, M. D. Anderson Cancer Center, Department of Molecular Genetics, Houston 77030, USA.
Park
R W
RW
D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics*; D016207:Cytokines / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins; D009928:Organ Specificity / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D016207:Cytokines; D004268:DNA-Binding Proteins; D006133:Growth Substances; D009363:Neoplasm Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D003094:Collagen