Myogenin Explained

Myogenin, is a transcriptional activator encoded by the MYOG gene.^[1] Myogenin is a muscle-specific basic-helix-loop-helix (bHLH) transcription factor involved in the coordination of skeletal muscle development or myogenesis and repair. Myogenin is a member of the MyoD family of transcription factors, which also includes MyoD, Myf5, and MRF4.

In mice, myogenin is essential for the development of functional skeletal muscle. Myogenin is required for the proper differentiation of most myogenic precursor cells during the process of myogenesis. When the DNA coding for myogenin was knocked out of the mouse genome, severe skeletal muscle defects were observed. Mice lacking both copies of myogenin (homozygous-null) suffer from perinatal lethality due to the lack of mature secondary skeletal muscle fibers throughout the body.^{[2] [3]}

In cell culture, myogenin can induce myogenesis in a variety of non-muscle cell types.

Interactions

Myogenin has been shown to interact with:

• MDFI,^[4]
• POLR2C,^[5]
• Serum response factor^[6]
• Sp1 transcription factor,^[7] and
• TCF3.^{[8] [9]}

Further reading

• Weintraub H, Davis R, Tapscott S, Thayer M, Krause M, Benezra R, Blackwell TK, Turner D, Rupp R, Hollenberg S . The myoD gene family: nodal point during specification of the muscle cell lineage . Science . 251 . 4995 . 761–6 . February 1991 . 1846704 . 10.1126/science.1846704 . 1991Sci...251..761W .
• Chakraborty T, Martin JF, Olson EN . Analysis of the oligomerization of myogenin and E2A products in vivo using a two-hybrid assay system . The Journal of Biological Chemistry . 267 . 25 . 17498–501 . September 1992 . 10.1016/S0021-9258(19)37069-3 . 1325437 . free .
• Funk WD, Wright WE . Cyclic amplification and selection of targets for multicomponent complexes: myogenin interacts with factors recognizing binding sites for basic helix-loop-helix, nuclear factor 1, myocyte-specific enhancer-binding factor 2, and COMP1 factor . Proceedings of the National Academy of Sciences of the United States of America . 89 . 20 . 9484–8 . October 1992 . 1329097 . 50156 . 10.1073/pnas.89.20.9484 . 1992PNAS...89.9484F . free .
• Lassar AB, Davis RL, Wright WE, Kadesch T, Murre C, Voronova A, Baltimore D, Weintraub H . Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo . Cell . 66 . 2 . 305–15 . July 1991 . 1649701 . 10.1016/0092-8674(91)90620-E . 25957022 .
• Salminen A, Braun T, Buchberger A, Jürs S, Winter B, Arnold HH . Transcription of the muscle regulatory gene Myf4 is regulated by serum components, peptide growth factors and signaling pathways involving G proteins . The Journal of Cell Biology . 115 . 4 . 905–17 . November 1991 . 1659574 . 2289955 . 10.1083/jcb.115.4.905 .
• Pearson-White SH . Human MyoD: cDNA and deduced amino acid sequence . Nucleic Acids Research . 19 . 5 . 1148 . March 1991 . 1850513 . 333794 . 10.1093/nar/19.5.1148 .
• Olson E, Edmondson D, Wright WE, Lin VK, Guenet JL, Simon-Chazottes D, Thompson LH, Stallings RL, Schroeder WT, Duvic M . Myogenin is in an evolutionarily conserved linkage group on human chromosome 1q31-q41 and unlinked to other mapped muscle regulatory factor genes . Genomics . 8 . 3 . 427–34 . November 1990 . 1962752 . 10.1016/0888-7543(90)90028-S .
• Brennan TJ, Olson EN . Myogenin resides in the nucleus and acquires high affinity for a conserved enhancer element on heterodimerization . Genes & Development . 4 . 4 . 582–95 . April 1990 . 2163343 . 10.1101/gad.4.4.582 . free .
• Braun T, Bober E, Buschhausen-Denker G, Kohtz S, Grzeschik KH, Arnold HH, Kotz S . Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products . The EMBO Journal . 8 . 12 . 3617–25 . December 1989 . 2583111 . 402043 . 10.1002/j.1460-2075.1989.tb08535.x.
• Groisman R, Masutani H, Leibovitch MP, Robin P, Soudant I, Trouche D, Harel-Bellan A . Physical interaction between the mitogen-responsive serum response factor and myogenic basic-helix-loop-helix proteins . The Journal of Biological Chemistry . 271 . 9 . 5258–64 . March 1996 . 8617811 . 10.1074/jbc.271.9.5258 . free .
• Chen CM, Kraut N, Groudine M, Weintraub H . I-mf, a novel myogenic repressor, interacts with members of the MyoD family . Cell . 86 . 5 . 731–41 . September 1996 . 8797820 . 10.1016/S0092-8674(00)80148-8 . 16252710 . free .
• Kong Y, Flick MJ, Kudla AJ, Konieczny SF . Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD . Molecular and Cellular Biology . 17 . 8 . 4750–60 . August 1997 . 9234731 . 232327 . 10.1128/mcb.17.8.4750 .
• Langlands K, Yin X, Anand G, Prochownik EV . Differential interactions of Id proteins with basic-helix-loop-helix transcription factors . The Journal of Biological Chemistry . 272 . 32 . 19785–93 . August 1997 . 9242638 . 10.1074/jbc.272.32.19785 . free .
• Biesiada E, Hamamori Y, Kedes L, Sartorelli V . Myogenic basic helix-loop-helix proteins and Sp1 interact as components of a multiprotein transcriptional complex required for activity of the human cardiac alpha-actin promoter . Molecular and Cellular Biology . 19 . 4 . 2577–84 . April 1999 . 10082523 . 84050 . 10.1128/MCB.19.4.2577.
• Tseng BS, Cavin ST, Hoffman EP, Iannaccone ST, Mancias P, Booth FW, Butler IJ . Human bHLH transcription factor gene myogenin (MYOG): genomic sequence and negative mutation analysis in patients with severe congenital myopathies . Genomics . 57 . 3 . 419–23 . May 1999 . 10329008 . 10.1006/geno.1998.5719 .
• Knoepfler PS, Bergstrom DA, Uetsuki T, Dac-Korytko I, Sun YH, Wright WE, Tapscott SJ, Kamps MP . A conserved motif N-terminal to the DNA-binding domains of myogenic bHLH transcription factors mediates cooperative DNA binding with pbx-Meis1/Prep1 . Nucleic Acids Research . 27 . 18 . 3752–61 . September 1999 . 10471746 . 148632 . 10.1093/nar/27.18.3752 .
• Onions J, Hermann S, Grundström T . A novel type of calmodulin interaction in the inhibition of basic helix-loop-helix transcription factors . Biochemistry . 39 . 15 . 4366–74 . April 2000 . 10757985 . 10.1021/bi992533u .
• Corbi N, Di Padova M, De Angelis R, Bruno T, Libri V, Iezzi S, Floridi A, Fanciulli M, Passananti C . The alpha-like RNA polymerase II core subunit 3 (RPB3) is involved in tissue-specific transcription and muscle differentiation via interaction with the myogenic factor myogenin . FASEB Journal . 16 . 12 . 1639–41 . October 2002 . 12207009 . 10.1096/fj.02-0123fje . free . 30243193 .

Notes and References

1. Web site: MYOG - Myogenin - Homo sapiens (Human) - MYOG gene & protein . www.uniprot.org . en.
2. Hasty P, Bradley A, Morris JH, Edmondson DG, Venuti JM, Olson EN, Klein WH . Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene . Nature . 364 . 6437 . 501–6 . August 1993 . 8393145 . 10.1038/364501a0 . 1993Natur.364..501H . 4372223 .
3. Nabeshima Y, Hanaoka K, Hayasaka M, Esumi E, Li S, Nonaka I, Nabeshima Y . Myogenin gene disruption results in perinatal lethality because of severe muscle defect . Nature . 364 . 6437 . 532–5 . August 1993 . 8393146 . 10.1038/364532a0 . 1993Natur.364..532N . 4055548 .
4. Chen CM, Kraut N, Groudine M, Weintraub H . I-mf, a novel myogenic repressor, interacts with members of the MyoD family . Cell . 86 . 5 . 731–41 . September 1996 . 8797820 . 10.1016/s0092-8674(00)80148-8 . 16252710 . free .
5. Corbi N, Di Padova M, De Angelis R, Bruno T, Libri V, Iezzi S, Floridi A, Fanciulli M, Passananti C . The alpha-like RNA polymerase II core subunit 3 (RPB3) is involved in tissue-specific transcription and muscle differentiation via interaction with the myogenic factor myogenin . FASEB Journal . 16 . 12 . 1639–41 . October 2002 . 12207009 . 10.1096/fj.02-0123fje . free . 30243193 .
6. Groisman R, Masutani H, Leibovitch MP, Robin P, Soudant I, Trouche D, Harel-Bellan A . Physical interaction between the mitogen-responsive serum response factor and myogenic basic-helix-loop-helix proteins . The Journal of Biological Chemistry . 271 . 9 . 5258–64 . March 1996 . 8617811 . 10.1074/jbc.271.9.5258 . free .
7. Biesiada E, Hamamori Y, Kedes L, Sartorelli V . Myogenic basic helix-loop-helix proteins and Sp1 interact as components of a multiprotein transcriptional complex required for activity of the human cardiac alpha-actin promoter . Molecular and Cellular Biology . 19 . 4 . 2577–84 . April 1999 . 10082523 . 84050 . 10.1128/MCB.19.4.2577.
8. Langlands K, Yin X, Anand G, Prochownik EV . Differential interactions of Id proteins with basic-helix-loop-helix transcription factors . The Journal of Biological Chemistry . 272 . 32 . 19785–93 . August 1997 . 9242638 . 10.1074/jbc.272.32.19785 . free .
9. Chakraborty T, Martin JF, Olson EN . Analysis of the oligomerization of myogenin and E2A products in vivo using a two-hybrid assay system . The Journal of Biological Chemistry . 267 . 25 . 17498–501 . September 1992 . 10.1016/S0021-9258(19)37069-3 . 1325437 . free .