αMHC and βMHC promote fast and slow contractility, respectively. TRs act through positive and negative TREs to activate and repress expression of the αMHC and βMHC genes, respectively, which are linked. Propylthiouracil (PTU) prevents T3 biosynthesis, resulting in hypothyroidism and upregulation of βMHC due to loss of the repressive action of the TR on the negative TRE. Stress signals also activate βMHC expression, at least in part through the TR. Developmental signals drive βMHC expression before birth through separate regulatory elements. miR-208, encoded by the αMHC gene, negatively regulates mRNA targets encoding THRAP1 and other negative regulators of βMHC expression. miR-208 also represses an activator of fast skeletal muscle genes. Modified with permission from Science (5).