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]

The SAP DNA-binding domain is shown in purple and spans amino acids 541–807. The basic region, in turquoise, spans amino acids 280-295. The glutamine-rich region, in brown, spans amino acids 321-346. The leucine zipper analog, shown in green, spans amino acids 513-556. Domains for binding of protein partners, MEF2C and HCAC5, are shown in magenta (spanning amino acids 12-27) and orange (spanning amino acids 153-205), respectively.

Structure

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.[12]

Function

Myocardin is a transcriptional coactivator, enhancing the activity of specific genes involved in smooth muscle development and function by interacting with transcription factor, SRF.[12][13][14] Myocardin can induce smooth muscle cell differentiation when it is expressed in appropriate cells.[15] Researchers have also found that myocardin plays a role in myocardial cell differentiation by inhibiting myocardin in Xenopus embryos.[13]

Amino acid residues 541–807 of myocardin are believed to play a key role in mediating its ability to activate transcription.[13] 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.[13] 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.[13]

Myocardin contributes to the expression of cardiac muscle cell differentiation by interacting with myocyte enhancer factor 2 (MEF2) or SRF, enhancing their transcriptional activity.[16] Conversely, in smooth muscle cells, myocardin associates with the transcriptional coactivator, p300, stimulting acetylation and consequent expression of smooth muscle cell genes, as well as acetylation of myocardin itself.[17][18] Class II HDAC proteins are responsible for histone deacetylation, and have been found to inhibit the activity of myocardin.[17]

Gene

There are four known transcript variants (isoforms) of the MYOCD gene.[16][19] While the exact function of each isoform is not well understood, it is suggested that each variant may have tissue-specific functions.[20] 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.[16]

Expression of MYOCD is specifically observed in the cardaic and smooth muscle tissues, such as the arteries, female reproductive organs and colon.[13][15][21] Expression is also observed in the heart, aorta, and bladder, tissues in which smooth muscle can be found.[15][22]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000141052 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020542 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, et al. (November 2002). "Potentiation of serum response factor activity by a family of myocardin-related transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 99 (23): 14855–14860. Bibcode:2002PNAS...9914855W. doi:10.1073/pnas.222561499. PMC 137508. PMID 12397177.
  6. ^ "MYOCD myocardin [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-04-07.
  7. ^ a b Wang Z, Wang DZ, Pipes GC, Olson EN (June 2003). "Myocardin is a master regulator of smooth muscle gene expression". Proceedings of the National Academy of Sciences of the United States of America. 100 (12): 7129–7134. Bibcode:2003PNAS..100.7129W. doi:10.1073/pnas.1232341100. PMC 165841. PMID 12756293.
  8. ^ a b c Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, et al. (June 2001). "Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor". Cell. 105 (7): 851–862. doi:10.1016/s0092-8674(01)00404-4. PMID 11439182.
  9. ^ Du KL, Ip HS, Li J, Chen M, Dandre F, Yu W, et al. (April 2003). "Myocardin is a critical serum response factor cofactor in the transcriptional program regulating smooth muscle cell differentiation". Molecular and Cellular Biology. 23 (7): 2425–2437. doi:10.1128/MCB.23.7.2425-2437.2003. PMC 150745. PMID 12640126.
  10. ^ Aravind L, Koonin EV (March 2000). "SAP - a putative DNA-binding motif involved in chromosomal organization". Trends in Biochemical Sciences. 25 (3): 112–114. doi:10.1016/s0968-0004(99)01537-6. PMID 10694879.
  11. ^ Hnízda A, Tesina P, Nguyen TB, Kukačka Z, Kater L, Chaplin AK, et al. (July 2021). "SAP domain forms a flexible part of DNA aperture in Ku70/80". The FEBS Journal. 288 (14): 4382–4393. doi:10.1111/febs.15732. PMC 8653891. PMID 33511782.
  12. ^ a b Wang Z, Wang DZ, Pipes GC, Olson EN (June 2003). "Myocardin is a master regulator of smooth muscle gene expression". Proceedings of the National Academy of Sciences of the United States of America. 100 (12): 7129–7134. Bibcode:2003PNAS..100.7129W. doi:10.1073/pnas.1232341100. PMC 165841. PMID 12756293.
  13. ^ a b c d e f Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, et al. (June 2001). "Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor". Cell. 105 (7): 851–862. doi:10.1016/s0092-8674(01)00404-4. PMID 11439182.
  14. ^ Long X, Tharp DL, Georger MA, Slivano OJ, Lee MY, Wamhoff BR, et al. (November 2009). "The smooth muscle cell-restricted KCNMB1 ion channel subunit is a direct transcriptional target of serum response factor and myocardin". The Journal of Biological Chemistry. 284 (48): 33671–33682. doi:10.1074/jbc.m109.050419. PMC 2785209. PMID 19801679.
  15. ^ a b c Du KL, Ip HS, Li J, Chen M, Dandre F, Yu W, et al. (April 2003). "Myocardin is a critical serum response factor cofactor in the transcriptional program regulating smooth muscle cell differentiation". Molecular and Cellular Biology. 23 (7): 2425–2437. doi:10.1128/MCB.23.7.2425-2437.2003. PMC 150745. PMID 12640126.
  16. ^ a b c Creemers EE, Sutherland LB, Oh J, Barbosa AC, Olson EN (July 2006). "Coactivation of MEF2 by the SAP domain proteins myocardin and MASTR". Molecular Cell. 23 (1): 83–96. doi:10.1016/j.molcel.2006.05.026. PMID 16818234.
  17. ^ a b Cao D, Wang Z, Zhang CL, Oh J, Xing W, Li S, et al. (January 2005). "Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin". Molecular and Cellular Biology. 25 (1): 364–376. doi:10.1128/MCB.25.1.364-376.2005. PMC 538763. PMID 15601857.
  18. ^ Cao D, Wang C, Tang R, Chen H, Zhang Z, Tatsuguchi M, et al. (November 2012). "Acetylation of myocardin is required for the activation of cardiac and smooth muscle genes". The Journal of Biological Chemistry. 287 (46): 38495–38504. doi:10.1074/jbc.m112.353649. PMC 3493894. PMID 23007391.
  19. ^ "Human hg19 chr17:12,543,845-12,696,012 UCSC Genome Browser v462". genome.ucsc.edu. Retrieved 2024-04-07.
  20. ^ Imamura M, Long X, Nanda V, Miano JM (September 2010). "Expression and functional activity of four myocardin isoforms". Gene. 464 (1–2): 1–10. doi:10.1016/j.gene.2010.03.012. PMID 20385216.
  21. ^ "GTEx Portal". www.gtexportal.org. Retrieved 2024-04-07.
  22. ^ Imamura M, Long X, Nanda V, Miano JM (September 2010). "Expression and functional activity of four myocardin isoforms". Gene. 464 (1–2): 1–10. doi:10.1016/j.gene.2010.03.012. PMID 20385216.

Further reading


Allikas: Https://en.wikipedia.org/wiki/Myocardin
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