Myogenic regulatory factors explained

Myogenic regulatory factors (MRF) are basic helix-loop-helix (bHLH) transcription factors that regulate myogenesis: MyoD, Myf5, myogenin, and MRF4.^[1]

These proteins contain a conserved basic DNA binding domain that binds the E box DNA motif.^[2] They dimerize with other HLH containing proteins through an HLH-HLH interaction.^[3]

MRF Gene Family Evolution

There are typically four vertebrate MRF paralogues which are homologous to typically a single MRF gene in non-vertebrates. These four genes are thought to have been duplicated in the two rounds of whole-genome duplication early in vertebrate evolution that played a role in the evolution of more complex vertebrate body plans. The four MRFs have four distinct expression profiles, though with some redundancy, as MyoD and Myf5 are both involved in myoblast determination, and are followed by the activation of Myf6 (MRF4) and Myog in myoblast differentiation.^[4] There have also been instances of independent duplication of the MRFs in invertebrate lineages, similarly followed by subfunctionalization of the expression of the genes in time and/or in space. In amphioxus, an invertebrate chordate closely related to vertebrates, there are five MRFs which are expressed in different patterns during development.^[5]

Notes and References

1. Perry R, Rudnick M . Molecular mechanisms regulating myogenic determination and differentiation . Front Biosci . 5 . D750–67 . 2000. 10966875 . 10.2741/Perry. free .
2. Weintraub H, Davis R, Tapscott S, Thayer M, Krause M, Benezra R, Blackwell T, Turner D, Rupp R, Hollenberg S . The myoD gene family: nodal point during specification of the muscle cell lineage . Science . 251 . 4995 . 761–6 . 1991 . 1846704 . 10.1126/science.1846704. 1991Sci...251..761W .
3. Barndt R, Zhuang Y . Controlling lymphopoiesis with a combinatorial E-protein code . Cold Spring Harb Symp Quant Biol . 64 . 45–50 . 1999. 11232321 . 10.1101/sqb.1999.64.45.
4. Hernández-Hernández J, García-González E, Brun C, Rudnicki M . The myogenic regulatory factors, determinants of muscle development, cell identity and regeneration . Seminars in Cell and Developmental Biology . 72 . 10–18 . 2017 . 29127045 . 10.1016/j.semcdb.2017.11.010 . free . 5723221 .
5. Aase-Remedios M, Coll-Lladó C, Ferrier D . More Than One-to-Four via 2R: Evidence of an Independent Amphioxus Expansion and Two-Gene Ancestral Vertebrate State for MyoD-Related Myogenic Regulatory Factors (MRFs) . Molecular Biology and Evolution . 2020 . 37 . 10 . 2966–2982 . 32520990 . 10.1093/molbev/msaa147. 7530620. free .