Affinage

MYF5

Myogenic factor 5 · UniProt P13349

Length
255 aa
Mass
28.3 kDa
Annotated
2026-04-29
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYF5 is a basic helix-loop-helix transcription factor that serves as one of the earliest determinants of skeletal muscle lineage commitment, functioning upstream of MyoD within a regulatory hierarchy controlled by Pax3, Dmrt2, Six1, Wnt/β-catenin, and Shh/Gli signaling (PMID:9094721, PMID:20368965, PMID:16936075, PMID:11782449). MYF5 heterodimerizes with E12/E47 to bind E-box elements via its basic-HLH domain and activates transcription through a C-terminal transactivation domain; genome-wide, it induces histone acetylation at target loci but, unlike MyoD, fails to recruit RNA Polymerase II efficiently, thereby specifying muscle identity without robust transcriptional activation of muscle structural genes (PMID:2385294, PMID:26906734). MYF5 and MyoD define genetically separable myogenic lineages—MYF5 acting preferentially in epaxial (paraspinal/intercostal) progenitors and MyoD in hypaxial (limb) progenitors—with either factor sufficient for skeletal muscle formation but both absolutely required for muscle regeneration (PMID:9428409, PMID:8617206, PMID:29478898). Beyond its role as a DNA-binding transcription factor, MYF5 also functions as an RNA-binding protein that promotes Cyclin D1 translation to sustain myoblast proliferation, and its translation in quiescent satellite cells is silenced by miR-31-mediated mRNA sequestration in mRNP granules (PMID:26819411, PMID:22770245).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1990 High

    Establishing that MYF5 possesses an intrinsic transactivation domain separate from its bHLH motif and requires E12 heterodimerization for high-affinity DNA binding resolved how a tissue-restricted bHLH factor achieves muscle-specific gene activation.

    Evidence GAL4 fusion transactivation assay and DNA-binding reconstitution with E12 in vitro

    PMID:2385294

    Open questions at the time
    • No endogenous target genes identified at this stage
    • Structural basis of E12-MYF5 heterodimer specificity unknown
  2. 1992 High

    Germline knockouts of Myf5 and MyoD independently revealed functional compensation between the two factors: Myf5-null mice form skeletal muscle (with delayed myotome and rib defects) while MyoD-null mice upregulate Myf5 and also form muscle, establishing that either factor alone is sufficient for myogenesis.

    Evidence Targeted gene disruption in mice with histological and Northern blot analysis

    PMID:1330322 PMID:1423602

    Open questions at the time
    • Whether compensation is direct transcriptional cross-regulation or selection of alternative progenitors was unresolved
    • Rib phenotype mechanism (direct vs. indirect role of Myf5) unclear
  3. 1993 High

    Demonstration that MYF5 transactivates the desmin promoter through E-box elements confirmed that canonical muscle structural genes are direct MYF5 targets via bHLH-E-box recognition.

    Evidence Co-transfection reporter assays and EMSA in 10T-1/2 fibroblasts

    PMID:8382796

    Open questions at the time
    • Only a single target gene tested
    • In vivo occupancy not yet demonstrated
  4. 1996 High

    Explant and ES cell ablation studies established that MYF5 and MyoD are activated in distinct mesenchymal progenitor populations responsive to different inductive signals (neural tube vs. dorsal ectoderm), defining two parallel myogenic lineages rather than a simple linear cascade.

    Evidence Paraxial mesoderm explants from Myf5-nlacZ mice; selective ablation of Myf5-expressing cells in ES cultures

    PMID:8617206 PMID:8625794

    Open questions at the time
    • Molecular identity of the distinct progenitor populations not characterized
    • Whether the two lineages contribute equally to adult muscle was unknown
  5. 1997 High

    Genetic epistasis with Pax3/Myf5 double-null mice and spatial analysis of single nulls resolved the upstream hierarchy: Pax3 and Myf5 define two independent pathways that both converge on MyoD activation, with Myf5 required for epaxial and MyoD for hypaxial muscle development.

    Evidence Double homozygous splotch×Myf5-nlacZ mutant analysis; Pax3 ectopic expression in embryos; Myf5/MyoD null comparisons

    PMID:9094721 PMID:9094722 PMID:9428409

    Open questions at the time
    • Whether Pax3 directly binds Myf5 regulatory elements was not yet shown
    • Signaling pathways upstream of Myf5 epaxial activation not identified
  6. 1997 High

    Knock-in of myogenin into the Myf5 locus rescued the rib phenotype, showing that the rib defect in Myf5-null mice reflects the spatiotemporal expression pattern of the locus rather than unique Myf5 protein functions.

    Evidence Gene knock-in of myogenin cDNA into Myf5 locus in mice

    PMID:8587605

    Open questions at the time
    • Whether all Myf5 functions are replaceable by myogenin was not addressed beyond rib formation
  7. 1998 High

    Discovery that Myf5 undergoes cell cycle-regulated mitotic phosphorylation and proteolytic degradation, while its protein oscillates out of phase with MyoD, introduced post-translational regulation as a key control layer for MRF activity in proliferating myoblasts.

    Evidence Synchronized myoblast cultures with immunoblotting and immunofluorescence; nocodazole block

    PMID:9425159 PMID:9744876

    Open questions at the time
    • Kinase responsible for mitotic phosphorylation not identified
    • Ubiquitin ligase mediating degradation unknown
    • Functional consequence of oscillation for differentiation decisions not tested
  8. 1998 High

    Wnt1 was identified as a preferential activator of the Myf5 pathway (and Wnt7a of MyoD), linking specific extracellular signals from the neural tube and ectoderm to the two parallel myogenic lineages.

    Evidence Paraxial mesoderm explants co-cultured with Wnt-expressing cells and scored with Myf5-nlacZ reporter

    PMID:9753670

    Open questions at the time
    • Whether Wnt1 acts directly on Myf5 regulatory elements or through intermediates was unknown
  9. 2002 High

    Identification of a Gli-binding site in the Myf5 epaxial somite enhancer demonstrated that Shh signals directly through Gli transcription factors to activate Myf5 in epaxial progenitors, providing the first cis-regulatory link between morphogen signaling and Myf5 transcription.

    Evidence Transgenic lacZ reporter with Gli site mutagenesis in Shh mutant embryos; luciferase reporter in Shh-responsive 3T3 cells

    PMID:11782449

    Open questions at the time
    • Which Gli family member is the primary activator in vivo not resolved
    • Interaction with other enhancer inputs (Wnt, Pax3) not yet dissected
  10. 2003 High

    Showing that p300 acetyltransferase activity is required upstream of Myf5 induction placed chromatin remodeling between Pax3 and Myf5 in the activation hierarchy.

    Evidence p300-null and p300 AT-null mouse embryos and ES cell differentiation assays

    PMID:14517256

    Open questions at the time
    • Whether p300 acts directly at the Myf5 locus or indirectly was not determined
  11. 2004 High

    An allelic series at the Myf5 locus revealed that Mrf4, which is linked to Myf5, also acts as a determination factor upstream of MyoD, revising the model from two to three parallel determination pathways (Myf5, Mrf4, and Pax3→MyoD).

    Evidence Allelic series of Myf5 targeted mutations differentially affecting Mrf4 expression; genetic epistasis in double/triple nulls

    PMID:15386014

    Open questions at the time
    • Whether Mrf4 and Myf5 have distinct or overlapping transcriptional targets genome-wide was unknown
  12. 2006 High

    Direct binding of Pax3, Six1/Six4, and Wnt/β-catenin effectors to defined cis-regulatory elements upstream of Myf5 completed the picture of how multiple signaling pathways converge on a modular Myf5 enhancer landscape to drive lineage- and region-specific expression.

    Evidence ChIP, EMSA, transgenic reporter mutagenesis at -57.5 kb element (Pax3 and Six1 sites) and epaxial enhancer (Tcf/Lef sites); Six1/4-null mice

    PMID:16936075 PMID:16951257 PMID:17592144

    Open questions at the time
    • How enhancer integration across modules is coordinated in time and space was not resolved
    • Chromatin architecture at the Myf5 locus not examined
  13. 2008 High

    Lineage tracing with conditional ablation confirmed that Myf5-expressing and Myf5-independent (MyoD) populations represent genuinely separate cell lineages in vivo, validating the two-lineage model at the clonal level.

    Evidence Cre-based lineage tracing and conditional diphtheria toxin ablation in mice

    PMID:18331721

    Open questions at the time
    • Relative contribution of each lineage to specific adult muscle groups not quantified
  14. 2010 High

    Identification of a Pax3→Dmrt2→Myf5 cascade operating in epaxial dermomyotome revealed an intermediate transcription factor relay between Pax3 and Myf5, adding resolution to the upstream hierarchy.

    Evidence Dmrt2-null embryos, ChIP, EMSA, and conditional overexpression of Dmrt2 in Pax3-expressing cells

    PMID:20368965

    Open questions at the time
    • Whether Dmrt2 is required in hypaxial progenitors was not tested
  15. 2012 High

    Discovery that miR-31 sequesters Myf5 mRNA in mRNP granules in quiescent satellite cells, with activation-triggered granule dissolution enabling rapid Myf5 translation, revealed a post-transcriptional gating mechanism controlling the quiescence-to-activation transition.

    Evidence mRNP granule fractionation, miR-31 overexpression/knockdown, ex vivo single-fiber and in vivo regeneration assays

    PMID:22770245

    Open questions at the time
    • Signals triggering granule dissociation not identified
    • Whether other MRF mRNAs are similarly sequestered was not examined
  16. 2013 High

    Zic1/Zic2 were shown to cooperate with Gli2 and Pax3 to synergistically activate the Myf5 epaxial somite enhancer, explaining how combinatorial transcription factor inputs achieve robust Myf5 induction in the dorsomedial somite.

    Evidence Co-immunoprecipitation (Zic2-Gli2), reporter transactivation assays with domain mutagenesis, Zic2 mutant embryos, ChIP

    PMID:21211521 PMID:24036067

    Open questions at the time
    • Structural basis of Zic-Gli synergy unknown
    • In vivo requirement for combined Zic + Pax3 not tested genetically
  17. 2016 High

    Genome-wide ChIP-seq comparison revealed that Myf5 and MyoD bind the same sites but Myf5 induces histone acetylation without Pol II recruitment, establishing Myf5 as a 'pioneer-like' factor that specifies chromatin state rather than directly driving transcription of muscle genes.

    Evidence ChIP-seq for Myf5, MyoD, histone acetylation, and Pol II; RNA-seq comparison

    PMID:26906734

    Open questions at the time
    • Mechanism by which Myf5 recruits acetyltransferases but not Pol II is unknown
    • Whether Myf5 chromatin priming is required for subsequent MyoD-driven activation not directly tested
  18. 2016 High

    The unexpected finding that MYF5 binds Cyclin D1 mRNA and promotes its translation revealed a non-canonical RNA-binding function that links MYF5 to cell cycle progression and myoblast proliferation, independent of its transcriptional activity.

    Evidence RIP, biotin-RNA pulldown, UV-crosslinking, gel shift, MYF5 silencing with CCND1 rescue in myoblasts

    PMID:26819411

    Open questions at the time
    • RNA-binding domain within MYF5 not mapped
    • Full spectrum of MYF5 RNA targets not determined
    • Whether RNA-binding and DNA-binding are mutually exclusive activities is unknown
  19. 2018 High

    Conditional double knockout of MyoD and Myf5 in satellite cells demonstrated an absolute requirement for at least one determination factor for muscle regeneration, establishing that no other MRF can substitute in the adult stem cell compartment.

    Evidence Satellite cell-specific conditional double KO with injury-induced regeneration assays

    PMID:29478898

    Open questions at the time
    • Whether Mrf4 can compensate if expressed at the satellite cell stage was not tested
    • Fate of dKO satellite cell progeny (apoptosis vs. transdifferentiation) not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the mechanism by which MYF5 induces histone acetylation without Pol II recruitment, the identity of the kinase and E3 ligase controlling its mitotic degradation, the structural basis of its RNA-binding activity, and how the chromatin state it establishes is handed off to MyoD for transcriptional activation.
  • Kinase and ubiquitin ligase for mitotic Myf5 degradation unidentified
  • MYF5 RNA-binding domain and full RNA target repertoire unmapped
  • Mechanism distinguishing Myf5 chromatin priming from MyoD transcriptional activation unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0003723 RNA binding 1 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 4 R-HSA-4839726 Chromatin organization 2
Partners
DMRT2DUX4CE12GLI2PAX3SIX1ZIC1ZIC2

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 MYF5 contains an intrinsic transcriptional activation domain distinct from its helix-loop-helix motif, located in the C-terminal half of the protein. High-affinity sequence-specific DNA binding requires hetero-oligomeric association with the enhancer-binding protein E12 to confer muscle-specific transactivation. GAL4 fusion transactivation assay, DNA binding with E12 heterodimerization Nature High 2385294
1992 Inactivation of MyoD in mice leads to up-regulation of Myf-5 mRNA in postnatal muscle, indicating that MyoD normally represses Myf-5 expression, and that Myf-5 can functionally compensate for MyoD loss to maintain apparently normal skeletal muscle development. Germline MyoD null mutation, Northern blot analysis Cell High 1330322
1992 Targeted inactivation of Myf-5 in mice causes absence of the major distal part of the ribs and perinatal death from respiratory failure, but skeletal muscle develops normally due to compensation by other MRF family members. Early myotomal cell appearance is delayed by several days in Myf5-null embryos. Homologous recombination in ES cells, germline null mutation, histology, Northern blot Cell High 1423602
1992 Adenovirus E1a inhibits Myf-5 transcriptional activity without preventing its DNA binding or nuclear accumulation. The carboxy-terminal transactivation domain and basic-HLH region of Myf-5 are targets for E1a inhibition, and Myf-5 is required for myogenin gene activation. E1a expression in L6 cells, reporter gene transactivation, DNA binding assays Genes & development High 1315706
1993 MYF5 (along with MyoD, myogenin, and MRF4) can transactivate the desmin gene through E-box elements in its promoter and enhancer when co-transfected into 10T-1/2 fibroblasts. Co-transfection, gel electrophoretic mobility shift assay (EMSA), CAT reporter assay Nucleic acids research High 8382796
1996 Myf5 and MyoD are activated in distinct myogenic cell lineages via separate inductive signals: the neural tube preferentially activates myogenesis through a Myf5-dependent pathway (medial paraxial mesoderm), while dorsal ectoderm activates myogenesis through a MyoD-dependent pathway (lateral paraxial mesoderm). Explant culture of paraxial mesoderm from myf5-nlacZ transgenic mice, immunostaining for Myf5 and MyoD Development (Cambridge, England) High 8625794
1996 Myf5 and MyoD are activated in distinct mesenchymal stem cell populations and determine different skeletal muscle cell lineages. Selective ablation of Myf5-expressing precursors from ES cells does not prevent MyoD-dependent muscle differentiation, and early Myf5-expressing progenitors do not develop into later MyoD-expressing cells even when Myf5 is inactivated. Selective cell ablation in ES cell cultures, differentiation assays The EMBO journal High 8617206
1997 Pax-3 and Myf-5 define two distinct upstream myogenic pathways, and MyoD activation is genetically downstream of both. In splotch/Myf-5 double homozygous mutants, body muscles are completely absent and MyoD is not activated, demonstrating epistatic hierarchy: Pax3 and Myf5 act upstream of MyoD. Genetic epistasis using double homozygous mutant mice (splotch × Myf5-nlacZ) Cell High 9094721
1997 Ectopic Pax-3 is sufficient to induce expression of MyoD, Myf-5, and myogenin in paraxial mesoderm, lateral plate mesoderm, and neural tube in the absence of inducing tissues, identifying Pax-3 as a direct upstream activator of both Myf-5 and MyoD. Retroviral infection of embryonic tissues with Pax-3 expression construct, in situ hybridization Cell High 9094722
1997 MyoD and Myf-5 have distinct roles in epaxial vs. hypaxial muscle development: Myf-5 is specifically required for paraspinal and intercostal (epaxial) muscle development, while MyoD is required for limb and brachial arch (hypaxial) myogenesis. Analysis of Myf-5 and MyoD null mutant embryos with immunohistochemistry and lacZ transgene expression Development (Cambridge, England) High 9428409
1997 Myogenin knocked into the Myf5 locus (replacing Myf5) rescues rib cage formation and viability in Myf5-null mice, demonstrating functional redundancy between Myf5 and myogenin for rib formation and showing that Myf5's role in rib development is not due to unique protein-target interactions but to its timing/location of expression. Gene knock-in (myogenin cDNA into Myf5 locus), germline analysis Nature High 8587605
1998 Wnt1 (from dorsal neural tube) preferentially activates the Myf5-dependent myogenic pathway, while Wnt7a (from dorsal ectoderm) preferentially activates the MyoD-dependent pathway, in explants of mouse paraxial mesoderm. Paraxial mesoderm explant culture with Wnt-expressing cells, Myf5-nlacZ reporter Development (Cambridge, England) High 9753670
1998 RhoA GTPase and serum response factor (SRF) selectively control MyoD expression without affecting Myf5, demonstrating that these two myogenic factors are regulated by distinct upstream signaling pathways in myoblasts. Dominant-negative RhoA, C3-transferase inhibition, SRF inactivation, promoter-reporter assays in C2 muscle cells Molecular biology of the cell High 9658178
1998 Myf-5 and MyoD undergo distinct cell cycle-specific expression profiles in proliferating myoblasts: Myf-5 protein is high in G0, decreases during G1, and reappears at end of G1 through mitosis; MyoD is absent in G0, peaks in mid-G1, and falls at G1/S. The cell cycle ratio of Myf-5 to MyoD correlates with differentiation capacity. Immunofluorescence, synchronized myoblast cultures, isolation of undifferentiated cells The Journal of cell biology High 9744876
1998 Myf5 undergoes cell cycle-regulated proteolytic degradation: in mitotic myoblasts, a phosphorylated form of Myf5 is specifically degraded, marking the first example of cell cycle-regulated degradation of a transcription factor. This mitotic destruction does not occur for MyoD. Immunoblotting of synchronized cultures, nocodazole block, phosphorylation analysis The Journal of cell biology High 9425159
1999 Sonic hedgehog (Shh) from the notochord/floor plate has an essential inductive function in activating Myf5 (but not MyoD) in epaxial somite cells. MyoD activation by Shh in presomitic mesoderm explants is defective in Myf5-null embryos, showing Myf5 is the direct target of Shh in epaxial myogenesis and acts upstream of MyoD in this pathway. Shh null embryos analysis, presomitic mesoderm explants, recombinant Shh protein treatment, Myf5-null background Development (Cambridge, England) High 10457014
2000 Quiescent adult satellite cells co-express CD34 and Myf5, establishing Myf5 as the earliest marker of myogenic commitment in quiescent satellite cells. All CD34-positive satellite cells also express beta-galactosidase from the Myf5-nlacZ locus, confirming that quiescent satellite cells are committed to myogenesis. Isolated myofiber preparation, immunostaining, Myf5-nlacZ heterozygous mice The Journal of cell biology High 11121437
2002 Myf5 is a direct target of long-range Shh signaling through positive regulation by Gli transcription factors. The Myf5 epaxial somite (ES) enhancer contains a Gli-binding site required for enhancer activation by Shh signaling both in transfected cells and in transgenic embryos. Transgenic lacZ reporter analysis, Shh mutant embryos, luciferase reporter in Shh-responsive 3T3 cells, Gli binding site mutagenesis Genes & development High 11782449
2004 Mrf4, not solely Myf5 and Myod, can confer skeletal muscle identity. Using an allelic series of Myf5 mutants that differentially affect linked Mrf4 expression, skeletal muscle is present in Myf5:Myod double-null mice only when Mrf4 is expressed, revising the epistatic hierarchy: both Myf5 and Mrf4 act upstream of Myod. Allelic series of Myf5 targeted mutations, double/triple null genetic analysis Nature High 15386014
2006 Pax3 directly activates Myf5 transcription in hypaxial somite myogenic progenitors through a 145-bp regulatory element at -57.5 kb from the Myf5 gene. A Pax3 consensus site within this element binds Pax3 in vitro and in vivo (ChIP), and mutation of this site abolishes transgene expression in vivo. Transgenic reporter analysis, EMSA, chromatin immunoprecipitation (ChIP), site-directed mutagenesis in vivo Genes & development High 16951257
2006 Canonical Wnt/beta-catenin signaling directly activates Myf5 in epaxial muscle progenitor cells via Tcf/Lef binding sites immediately 5' of the Myf5 early epaxial enhancer, acting synergistically with the Shh/Gli pathway. Activated beta-catenin is sufficient to activate Myf5 in somites. Blocking/activating beta-catenin in somite progenitors, transgenic reporter analysis with Tcf/Lef site mutagenesis Development (Cambridge, England) High 16936075
2006 Six1 and Six4 homeoproteins directly activate Myf5 transcription in embryonic limb buds through binding to a conserved site within the 145-bp regulatory element at -57.5 kb. Six1 binds this site in EMSA and ChIP assays and transactivates a reporter; mutation of the Six binding site impairs expression in limbs and somites. Six1/4 null mouse analysis, EMSA, ChIP, transgenic reporter with site mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 17592144
2008 Lineage tracing demonstrates the existence of two distinct myogenic cell lineages: a Myf5-expressing lineage and a Myf5-independent lineage. Ablation of the Myf5 lineage is compatible with myogenesis sustained by Myf5-independent, MyoD-expressing myoblasts, confirming that Myf5 and MyoD define separate cell lineages. Lineage tracing and conditional cell ablation in mice Developmental cell High 18331721
2010 A Pax3/Dmrt2/Myf5 regulatory cascade operates in epaxial dermomyotome stem cells. Pax3 directly activates Dmrt2 (confirmed by EMSA, ChIP, and transgenic analysis), and Dmrt2 in turn directly activates Myf5 through its early epaxial enhancer by binding to DM-domain sites; conditional Dmrt2 overexpression in Pax3-expressing cells activates Myf5. EMSA, ChIP, transgenic reporter with site mutagenesis, Dmrt2 KO, conditional overexpression PLoS genetics High 20368965
2012 In quiescent satellite cells, Myf5 mRNA is sequestered in mRNP granules together with microRNA-31, which suppresses its translation. Upon satellite cell activation, mRNP granules dissociate, miR-31 levels decrease, and Myf5 protein accumulates via translation of pre-existing mRNA. Manipulation of miR-31 levels affects satellite cell differentiation and muscle regeneration. mRNP granule fractionation, miR-31 manipulation (overexpression/knockdown), ex vivo and in vivo regeneration assays Cell stem cell High 22770245
2016 Myf5 and MyoD bind the same genomic sites genome-wide but have distinct molecular activities: Myf5 induces histone acetylation without Pol II recruitment or robust gene activation, while MyoD induces histone acetylation, recruits Pol II, and robustly activates transcription. Thus, Myf5 specifies the muscle lineage without significant transcriptional induction of muscle genes. ChIP-seq, RNA-seq, comparison of Myf5 vs. MyoD genome-wide binding and transcriptional output Developmental cell High 26906734
2016 MYF5 functions as an RNA-binding protein (in addition to a transcription factor), binding the 3' UTR and coding region of Ccnd1 (Cyclin D1) mRNA to enhance its translation. MYF5 silencing reduces CCND1 protein levels and myoblast proliferation, and restoring CCND1 partially rescues myogenesis after MYF5 knockdown. RIP (ribonucleoprotein immunoprecipitation), biotin-RNA pulldown, UV-crosslinking, gel shift, MYF5 silencing, CCND1 rescue Nucleic acids research High 26819411
2003 p300 acetyltransferase activity is specifically required upstream of Myf5 and MyoD for myogenesis in vivo. In p300-null mouse embryos, Myf5 induction is severely attenuated; ES cells homozygous for p300 AT-null or p300-null mutations fail to activate Myf5 and MyoD efficiently, while Pax3 (upstream of these MRFs) is expressed normally. p300 null/AT-null mouse embryos, ES cell differentiation assays, Northern blot The EMBO journal High 14517256
2009 DUX4c overexpression induces MYF5 protein and its DNA-binding activity in human myoblasts. DUX4c and MYF5 physically interact (co-immunoprecipitation), suggesting DUX4c stabilizes MYF5 protein, promoting myoblast proliferation. Western blot, DNA-binding assay, co-immunoprecipitation PloS one Medium 19829708
2013 Zic2 co-immunoprecipitates with Gli2, forming complexes that promote Myf5 epaxial somite enhancer activation. Zic1 and Zic2 (but not Zic3) potentiate Gli-dependent Myf5 ES enhancer transactivation in reporter assays, and Myf5 expression is delayed in Zic2 mutant embryos. Co-immunoprecipitation, reporter transactivation assay, Zic2 mutant embryos, presomitic mesoderm explants Developmental biology High 21211521
2013 Pax3 synergizes with Gli2 and Zic1 to transactivate the Myf5 epaxial somite (ES) enhancer. This synergy depends on conserved functional domains of the proteins, a homeodomain motif in the Myf5 promoter, and the Gli motif in the ES enhancer. Overexpression of Zic1 and Pax3 in mesodermal cells induces Myf5 expression with enrichment at the endogenous Myf5 locus (ChIP). Transactivation reporter assays, domain mutagenesis, ChIP, 10T1/2 cell overexpression Developmental biology High 24036067
2018 Satellite cells lacking both MyoD and Myf5 (double knockout) fail to undergo muscle differentiation after injury despite being maintained in uninjured muscle. dKO satellite cell progeny accumulate in damaged muscle but do not differentiate, demonstrating an absolute requirement for either MyoD or Myf5 in muscle regeneration and in stabilizing myogenic identity. Satellite cell-specific double conditional KO, muscle injury/regeneration assay, marker analysis Stem cell reports High 29478898
2018 SNAIL transcription factor binds the MYF5 promoter to suppress its expression in alveolar rhabdomyosarcoma (ARMS) cells. SNAIL silencing allows re-expression of MYF5, restores canonical MYOD binding at E-box sequences, and induces myogenic differentiation. SNAIL forms a repressive complex with HDAC1/2. ChIP, promoter analysis, SNAIL silencing, E-box occupancy assays, xenograft model Cell death & disease Medium 29844345

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell 831 1330322
2000 Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. The Journal of cell biology 680 11121437
1997 Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and Myf-5 act upstream of MyoD. Cell 667 9094721
2017 Function of the myogenic regulatory factors Myf5, MyoD, Myogenin and MRF4 in skeletal muscle, satellite cells and regenerative myogenesis. Seminars in cell & developmental biology 607 29127046
1992 Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. Cell 600 1423602
1991 Early expression of the myogenic regulatory gene, myf-5, in precursor cells of skeletal muscle in the mouse embryo. Development (Cambridge, England) 511 1652425
2004 Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice. Nature 484 15386014
1997 Ectopic Pax-3 activates MyoD and Myf-5 expression in embryonic mesoderm and neural tissue. Cell 356 9094722
1998 Cell heterogeneity upon myogenic differentiation: down-regulation of MyoD and Myf-5 generates 'reserve cells'. Journal of cell science 328 9472005
1999 In vivo satellite cell activation via Myf5 and MyoD in regenerating mouse skeletal muscle. Journal of cell science 323 10444384
1998 Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5. Development (Cambridge, England) 319 9753670
2012 Muscle satellite cells are primed for myogenesis but maintain quiescence with sequestration of Myf5 mRNA targeted by microRNA-31 in mRNP granules. Cell stem cell 274 22770245
2012 PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors. Cell metabolism 272 22940198
1998 The muscle regulatory factors MyoD and myf-5 undergo distinct cell cycle-specific expression in muscle cells. The Journal of cell biology 253 9744876
1997 MyoD and Myf-5 differentially regulate the development of limb versus trunk skeletal muscle. Development (Cambridge, England) 232 9428409
1999 Sonic hedgehog controls epaxial muscle determination through Myf5 activation. Development (Cambridge, England) 222 10457014
2006 A novel genetic hierarchy functions during hypaxial myogenesis: Pax3 directly activates Myf5 in muscle progenitor cells in the limb. Genes & development 211 16951257
1996 Activation of different myogenic pathways: myf-5 is induced by the neural tube and MyoD by the dorsal ectoderm in mouse paraxial mesoderm. Development (Cambridge, England) 182 8625794
2007 A role for the myogenic determination gene Myf5 in adult regenerative myogenesis. Developmental biology 174 17961534
2002 Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification. Genes & development 160 11782449
1991 Developmental patterns in the expression of Myf5, MyoD, myogenin, and MRF4 during myogenesis. The New biologist 157 1911647
1995 Inactivation of Myf-6 and Myf-5 genes in mice leads to alterations in skeletal muscle development. The EMBO journal 151 7720708
2006 The Wnt/beta-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis. Development (Cambridge, England) 147 16936075
2000 Delta 1-activated notch inhibits muscle differentiation without affecting Myf5 and Pax3 expression in chick limb myogenesis. Development (Cambridge, England) 140 11060246
2003 Differential role of p300 and CBP acetyltransferase during myogenesis: p300 acts upstream of MyoD and Myf5. The EMBO journal 132 14517256
1996 Gene targeting the myf-5 locus with nlacZ reveals expression of this myogenic factor in mature skeletal muscle fibres as well as early embryonic muscle. Developmental dynamics : an official publication of the American Association of Anatomists 130 8896984
2018 Loss of MyoD and Myf5 in Skeletal Muscle Stem Cells Results in Altered Myogenic Programming and Failed Regeneration. Stem cell reports 127 29478898
1996 Functional redundancy of the muscle-specific transcription factors Myf5 and myogenin. Nature 126 8587605
1990 Transcriptional activation domain of the muscle-specific gene-regulatory protein myf5. Nature 117 2385294
1995 Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis. Developmental biology 116 7589813
2008 Two cell lineages, myf5 and myf5-independent, participate in mouse skeletal myogenesis. Developmental cell 113 18331721
2000 The expression of Myf5 in the developing mouse embryo is controlled by discrete and dispersed enhancers specific for particular populations of skeletal muscle precursors. Development (Cambridge, England) 112 10934019
1998 RhoA GTPase and serum response factor control selectively the expression of MyoD without affecting Myf5 in mouse myoblasts. Molecular biology of the cell 108 9658178
2007 The myogenic factor Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification. Stem cells (Dayton, Ohio) 107 17495111
1998 Cell cycle-regulated expression of the muscle determination factor Myf5 in proliferating myoblasts. The Journal of cell biology 104 9425159
2000 Modular long-range regulation of Myf5 reveals unexpected heterogeneity between skeletal muscles in the mouse embryo. Development (Cambridge, England) 99 11003844
2000 Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4. Developmental biology 98 10694423
1993 Regulation of the mouse desmin gene: transactivated by MyoD, myogenin, MRF4 and Myf5. Nucleic acids research 95 8382796
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