Myocardin is a protein that in humans is encoded by the MYOCD gene. [5] [6] [7] [8]
Myocardin is a smooth muscle cell and cardiac muscle cell-specific transcriptional coactivator of serum response factor (SRF). [7] [8] When expressed in smooth muscle precursor cells and abnormally in nonmuscle cells, myocardin can induce smooth muscle cell differentiation. [9] Myocardin can also function in the differentiation of myocardial cells. [8]
Myocardin consists of four distinct regions, one of which is the SAF-A/B, Acinus, and PIAS (SAP) domain. [5] SAP domains are highly conserved motifs containing alpha helices that generally contain hydrophobic, polar, and bulky amino acids. [10] [11]
Myocardin also contains a basic region and a glutamine-rich region believed to be involved in binding SRF. [5]
Through a series of deletion mutations, researchers have also identified a dimerization motif spanning amino acid residues 513–713, containing an alpha helical leucine zipper analog between residues 513-556. [7]
Myocardin is a transcriptional coactivator, enhancing the activity of specific genes involved in smooth muscle development and function by interacting with transcription factor, SRF. [7] [8] [12] Myocardin can induce smooth muscle cell differentiation when it is expressed in appropriate cells. [9] Researchers have also found that myocardin plays a role in myocardial cell differentiation by inhibiting myocardin in Xenopus embryos. [8]
Amino acid residues 541–807 of myocardin are believed to play a key role in mediating its ability to activate transcription. Upon its initial discovery, researchers fused myocardin with the well studied GAL 4 transcription factor and examined how the regulation of GAL4-associated genes was affected. Myocardin is believed to activate transcription by binding to CArG box regions of DNA, characterized by the sequence CC(A/T)6GG, of muscle function genes, because mutations to these regions have led to an observed reduction in their sensitivity to myocardin. [8]
Myocardin contributes to the expression of cardiac muscle cell differentiation by interacting with myocyte enhancer factor 2 (MEF2) or SRF, enhancing their transcriptional activity. [13] Conversely, in smooth muscle cells, myocardin associates with the transcriptional coactivator, p300, stimulating acetylation and consequent expression of smooth muscle cell genes, as well as acetylation of myocardin itself. [14] [15] Class II HDAC proteins are responsible for histone deacetylation, and have been found to inhibit the activity of myocardin. [14]
There are four known transcript variants (isoforms) of the MYOCD gene. [13] [16] While the exact function of each isoform is not well understood, it is suggested that each variant may have tissue-specific functions. [17] Real-time polymerase chain reaction (RT-PCR) have realved two tissue-specific isoforms, myocardin-856, expressed in smooth muscle and found to interact with SRF, and myocardin-935, expressed in cardiac muscle and found to interact with either MEF2 or SRF. [13]
Expression of MYOCD is specifically observed in the cardaic and smooth muscle tissues, such as the arteries, female reproductive organs and colon. [8] [9] [18] Expression is also observed in the heart, aorta, and bladder, tissues in which smooth muscle can be found. [9] [17]
