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Intergenic Bidirectional Promoter of Cardiac Myosin Heavy Chain (MHC) Genes in Rats
Author(s) -
Giger Julia M,
Baldwin Kenneth M,
Haddad Fadia
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.989.20
Subject(s) - gene isoform , biology , gene , promoter , myh6 , myosin , intergenic region , microbiology and biotechnology , genetics , skeletal muscle , major histocompatibility complex , reporter gene , transcription (linguistics) , myh7 , gene expression , anatomy , linguistics , philosophy , genome
The rat heart expresses two MHC isoforms: beta (b) and alpha (a); these genes are arranged in tandem on the chromosome. We have hypothesized that there is an intergenic bidirectional promoter between these two genes that both promotes transcription of the a isoform and natural antisense of the b isoform. This intergenic bidirectional promoter may hold the key to the coordinated and antithetical regulation of a and b MHC genes that has been long recognized in the field of cardiac muscle regulation. Using a method of in vivo injection of promoter‐reporter plasmids, we have tested promoter activities of intergenic sequence in antisense and sense direction and found that activity requires an intact NF1 site! In fact, NF1 mutation caused a dramatic decrease in activity of the full length alpha promoter, which is very active in rat heart. NF1 site, is not conserved in the sequence of larger mammals. This is especially noteworthy because there is a divergence of b MHC expression in large vs. small mammals: the human and “large” mammals express the b isoform primarily in ventricular muscle whereas the small rodents, eg. the rat, express the a isoform primarily. Yet, both humans and rats express the beta MHC in “slow” fibers of skeletal muscles. To further understand the regulation of isoforms genes, we also tested tissue‐specificity and species specificity of alpha MHC promoter in rat skeletal muscle and heart. Supported by ADA and NIHHBL