Open AccessCArG boxes in the human cardiac alpha-actin gene are core binding sites for positive trans-acting regulatory factors.
Author(s) -
Takeshi Miwa,
Linda M. Boxer,
Larry Kedes
Publication year - 1987
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.84.19.6702
Subject(s) - biology , gene , actin , regulatory sequence , promoter , binding site , gene expression , microbiology and biotechnology , regulation of gene expression , cardiac muscle , transcriptional regulation , transcription factor , genetics , anatomy
Positively acting, rate-limiting regulatory factors that influence tissue-specific expression of the human cardiac alpha-actin gene in a mouse muscle cell line are shown by in vivo competition and gel mobility-shift assays to bind to upstream regions of its promoter but to neither vector DNA nor a beta-globin promoter. Although the two binding regions are distinctly separated, each corresponds to a cis region required for muscle-specific transcriptional stimulation, and each contains a core CC(A + T-rich)6GG sequence (designated CArG box), which is found in the promoter regions of several muscle-associated genes. Each site has an apparently different binding affinity for trans-acting factors, which may explain the different transcriptional stimulation activities of the two cis regions. Therefore, we conclude that the two CArG box regions are responsible for muscle-specific transcriptional activity of the cardiac alpha-actin gene through a mechanism that involves their binding of a positive trans-acting factor in muscle cells.