The alpha- and beta-myosin genes extend over 51 kb on chromosome 14 in human and 11 in mouse separated by about 4. 5 kb of intergenic sequence. They are located in tandem in the order of their expression during development. Transcription of each gene is independently controlled but coordinately regulated. During each embryogenesis, the beta-MHC gene is expressed as part of the cardiac myogenic program under the control of NKX-2. 5, MEF-2C, and GATA-4/5/6. After birth, thyroid hormone induces expression of alpha-MHC mRNA and inhibits expression of the beta-MHC gene. While a large number of physiological stimuli are capable of modifying this basic paradigm, thyroid hormone is required for expression of alpha-MHC in ventricular muscle. The positive TRE for T(3)-stimulation of alpha-MHC is an imperfect direct repeat located in the proximal promoter of the gene. The negative TRE for the beta-MHC gene is probably a binding half-site that is located adjacent to the TATA box. Binding of TEF-1 to a strong positive element in the proximal promoter is important in basal expression of beta-MHC gene and in the response to alpha(1)-adrenergic stimulation. The beta-MHC gene also is induced together with several other "fetal" genes during cardiac hypertrophy by a mechanism involving Ca(2+)-mediated activation of calcineurin and NF-AT3. Upon activation, NF-AT3 translocates to the nucleus and interacts with GATA-4 to stimulate beta-MHC expression. Changes in chromatin structure mediated by the association of histone acetylases and deacetylases with transcription factors are essential in regulating cell-specific expression of MHC genes. VSports手机版.