Transcriptional regulation of the human nonmuscle myosin II heavy chain-A gene. Identification of three clustered cis-elements in intron-1 which modulate transcription in a cell type- and differentiation state-dependent manner.
Abstract
In an attempt to identify cis-acting elements for transcriptional regulation of the human nonmuscle myosin II heavy chain (MHC)-A gene, the region extending 20 kilobases (kb) upstream and 40 kb downstream from the transcription start sites, which includes the entire 37-kb intron 1, was examined. Using transient transfection analysis of luciferase reporter constructs, a 100-base pair (bp) region (N2d) in intron 1, located 23 kb downstream from the transcriptional start sites, has been found to activate transcription in a cell type- and differentiation state-dependent manner. Maximum activity (approximately 20-fold) is seen in NIH 3T3 fibroblasts and intermediate activity (7-fold) in proliferating and undifferentiated C2C12 myoblasts. In contrast, this region is almost inactive in terminally differentiated C2C12 myotubes, in which endogenous nonmuscle MHC-A expression is down-regulated. Gel mobility shift assays and methylation interference analyses were performed using NIH 3T3 nuclear extracts to determine the protein-binding elements for transcription factors. Three binding elements have been identified within the N2d region. Antibody-supershift experiments, as well as competition experiments using consensus binding sequences f...Continue Reading
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