@article{63ee6db4341d4ecc9177f1adfb58c37f,
title = "A repressor region in the human β-myosin heavy chain gene that has a partial position dependency",
abstract = "Expression of the human β-myosin heavy chain (βMHC) gene was studied by transient assay in culture and in situ by direct injection of plasmids into adult rat hearts. In this report we describe a unique repressor region located -326/-309 (5′-TTGGTGGTCGTGGTCAGT-3′) of the human βMHC gene that is conserved among the rat, rabbit, and human βMHC genes. This sequence conferred repression onto heterologous promoters when the sequence was located 5′ but not 3′ to the promoters. This partial positional dependency suggests that the factor may act by limiting the binding of enhancers, located more proximally, to their DNA binding sites.",
author = "Edwards, {J. G.} and Bahl, {J. J.} and I. Flink and J. Milavetz and S. Goldman and E. Morkin",
note = "Funding Information: elements. This idea is supported by comparing the results of pax289 with pX2 (2). Both constructs had mutations in the Bfl binding region but the additional 5' flanking sequence prevented the remarkable fall in activity pax289 that the pX2 construct demonstrated. This suggests that the /3fl site may have been blocked by trans-factors binding to upstream sequence (2). Alternatively, the repressor may have directly inhibited the transcriptional complex. However, this latter explanation seems less likely since no inhibition was observed when the repressor region was located 3' to the promoter elements (Figure 2). Shimizu et al have suggested that the @fl and the AP2/NFe-like regions may act synergistically to increase expression (4). this is true then limiting access to either site will strongly influence constitutive expression. We have identified a negative element that located the three enhancer/promoter regions that regulate constitutive expression of the PMHC gene in the myocardium and skeletal muscle. In the human /3MHC gene, the region is located approximately -332 to -300 from the start of transcription. cis-element contains a GGT motif which is dissimilar to other known repressors and to date no factor has been identified that specifically regulates expression through this site. The cohere trans-acting factor(s) may be muscle specific since the region appears functional only in muscle tissue or cell lines. The region transduces its effect independent of promoter type when located 5' to the promoter elements. Collectively, the data is consistent with the concept, that a site dependent trans-acting factor(s) may act by blocking the binding of transcriptional activators in the pMHC 5'-flanking region. This may in part regulate expression of the pMHC gene.",
year = "1992",
month = nov,
day = "30",
doi = "10.1016/0006-291X(92)91586-F",
language = "English (US)",
volume = "189",
pages = "504--510",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",
}