Affinage

PAX7

Paired box protein Pax-7 · UniProt P23759

Length
505 aa
Mass
55.1 kDa
Annotated
2026-04-29
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAX7 is a paired box/homeodomain pioneer transcription factor that governs the identity, survival, and self-renewal of muscle satellite cells, specifies neural crest and pituitary melanotrope lineages, and when disrupted contributes to rhabdomyosarcoma. PAX7 opens chromatin at composite paired+homeodomain enhancers independently of DNA methylation status, establishing stable epigenetic memory that permits subsequent binding by non-pioneer factors; this pioneer activity requires both DNA-binding domains within the same molecule (PMID:23070814, PMID:29358650, PMID:34197620). In satellite cells, Carm1-mediated arginine methylation of PAX7 recruits MLL1/2-containing H3K4 methyltransferase complexes (via the adaptor Pax3/7BP–WDR5) to activate target genes such as Myf5 and Id3, while MYST1/SIRT2-regulated acetylation tunes homeodomain-motif binding specificity to control asymmetric division and stem cell pool size (PMID:22863532, PMID:22862948, PMID:34059674). PAX7 protein levels are tightly controlled by stabilizing CK2 phosphorylation at S201, essential SUMOylation at K85, and degradation via caspase-3 cleavage and NEDD4-mediated ubiquitination, while upstream transcriptional inputs from Notch–RBPJκ, TNF–p38α–PRC2, NF-κB, and post-transcriptional repression by miR-206/miR-133b collectively balance satellite cell self-renewal against myogenic differentiation (PMID:26372956, PMID:27144531, PMID:26304770, PMID:20887952, PMID:22493066, PMID:21041476).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1990 Medium

    Establishing PAX7's domain architecture and embryonic expression pattern revealed it as a paired box/homeodomain transcription factor expressed in both CNS and muscle lineages, raising the question of its developmental function.

    Evidence Northern blot and in situ hybridization in mouse embryos

    PMID:1982921

    Open questions at the time
    • No functional data; expression pattern alone
    • No DNA-binding target information
  2. 1994 High

    Identification of the PAX7-FKHR fusion in alveolar rhabdomyosarcoma demonstrated that PAX7's DNA-binding domains, when fused to a strong transactivation domain, drive oncogenesis, implicating PAX7's transcriptional targets in tumorigenesis.

    Evidence RT-PCR and sequencing of fusion transcripts from tumor samples; subsequent domain analysis showed PAX7-FKHR escapes cis-repression yielding ~600-fold activation

    PMID:10439042 PMID:8187070

    Open questions at the time
    • Endogenous PAX7 transcriptional targets unidentified
    • Mechanism of fusion-driven transformation not resolved
  3. 1996 High

    Pax7-null mice revealed an essential role in cephalic neural crest development, establishing that Pax7 is not redundant with Pax3 in craniofacial morphogenesis.

    Evidence Homologous recombination gene knockout in mice with histological analysis

    PMID:8631261

    Open questions at the time
    • Muscle satellite cell phenotype not yet examined in detail
    • Molecular targets mediating neural crest function unknown
  4. 2004 High

    Two key studies showed that Pax7 is required for postnatal satellite cell renewal and survival but cannot fully substitute for Pax3 in long-range muscle progenitor migration, delineating non-overlapping functions of the two paralogs.

    Evidence Pax7-null mouse satellite cell analysis; Pax7-into-Pax3 knock-in with assessment of limb muscle migration and c-Met activation

    PMID:15132998 PMID:15282552

    Open questions at the time
    • Mechanism of Pax7-dependent satellite cell survival unknown
    • Whether Pax7 directly regulates anti-apoptotic genes unresolved
  5. 2005 High

    Lineage tracing and double-mutant analysis established that Pax3+/Pax7+ progenitors are the resident muscle stem cells throughout embryonic and fetal development, and that Pax7 specifically protects satellite cells from apoptosis — a function Pax3 cannot substitute.

    Evidence GFP reporter at Pax3 locus; Pax3/Pax7 double-mutant mice; dominant-negative Pax7 constructs in satellite cells; apoptosis assays

    PMID:15843801 PMID:16380438

    Open questions at the time
    • Direct transcriptional targets mediating anti-apoptotic function not identified
    • Chromatin mechanism of Pax7 action uncharacterized
  6. 2006 High

    Neural crest specification was shown to require Pax7 during gastrulation, expanding its role beyond postnatal satellite cells to an early embryonic pioneer of neural crest identity.

    Evidence Morpholino knockdown in chick embryos with assessment of neural crest markers Slug, Sox9, Sox10, HNK-1

    PMID:16688176

    Open questions at the time
    • Mechanism of Pax7-dependent neural crest specification at chromatin level unknown
    • Whether Pax7 acts as pioneer factor in neural crest not tested
  7. 2007 High

    A cross-inhibitory relationship between Pax7 and myogenin was identified: Pax7 blocks MyoD function to prevent differentiation, while myogenin directly represses Pax7 transcription, establishing the molecular toggle governing satellite cell fate decisions.

    Evidence Pax7 overexpression plus MyoD function analysis in primary myoblasts; myogenin binding at Pax7 promoter by ChIP

    PMID:17548510 PMID:22328527

    Open questions at the time
    • Whether Pax7 repression of MyoD is transcription-independent or not fully resolved
    • Upstream signals selecting one arm of the toggle not yet integrated
  8. 2009 High

    Id3 was identified as a direct Pax7 transcriptional target in quiescent satellite cells, providing the first molecular link between Pax7 binding and suppression of premature differentiation.

    Evidence ChIP of Pax7 at Id3 promoter; luciferase reporter with binding site mutagenesis; Pax7 shRNA

    PMID:19458195

    Open questions at the time
    • Full complement of Pax7 target genes in satellite cells unknown
    • Chromatin-level mechanism of activation not characterized
  9. 2010 High

    Two upstream regulatory circuits controlling Pax7 levels were elucidated: TNF–p38α–EZH2/PRC2-mediated H3K27 trimethylation represses the Pax7 promoter during differentiation, while miR-206/miR-486 directly target the Pax7 3′UTR to form a bistable self-renewal/differentiation switch.

    Evidence Phosphorylation/Co-IP/ChIP of p38α–EZH2–YY1–PRC2 at Pax7 promoter; 3′UTR luciferase reporters for miR-206/miR-486 with miRNA-resistant Pax7 rescue

    PMID:20887952 PMID:21041476

    Open questions at the time
    • Integration of p38 and miRNA pathways in single cells not demonstrated
    • Whether these pathways act sequentially or in parallel unclear
  10. 2012 High

    A burst of mechanistic work revealed how Pax7 activates target genes: Carm1-dependent arginine methylation recruits MLL1/2 H3K4 methyltransferase complexes (bridged by Pax3/7BP–WDR5) to loci like Myf5 during asymmetric satellite stem cell divisions, while genome-wide ChIP-seq showed Pax7 occupies a far larger enhancer repertoire than Pax3 with preferential homeodomain-motif binding.

    Evidence In vitro methylation assays; Co-IP of Carm1–Pax7 and Pax3/7BP–WDR5; ChIP at Myf5; genome-wide ChIP-seq comparing Pax7 vs Pax3; DNA binding affinity measurements

    PMID:22609161 PMID:22862948 PMID:22863532

    Open questions at the time
    • Whether Carm1 methylation is regulated by upstream signals unknown
    • Structural basis for Pax7–MLL1/2 interaction unresolved
  11. 2012 High

    Pax7 was demonstrated to function as a pioneer transcription factor in pituitary melanotrope cells, opening chromatin at enhancers to redirect the Tpit-dependent transcriptional program from corticotrope to melanotrope identity, establishing a paradigm for Pax7 pioneer activity beyond muscle.

    Evidence Pax7 KO in pituitary; genome-wide ChIP and chromatin accessibility analysis

    PMID:23070814

    Open questions at the time
    • Whether Pax7 pioneer activity operates similarly in satellite cells not shown
    • Nucleosome remodeling mechanism unresolved
  12. 2012 High

    Notch signaling was shown to directly activate Pax7 transcription via RBPJκ binding upstream of Pax7, and SUMOylation at K85 was identified as essential for Pax7 transactivation and neural crest function, adding two new regulatory inputs.

    Evidence ChIP of RBPJκ at Pax7; NICD overexpression in MyoD−/− myoblasts; K85R SUMOylation-deficient mutant with in vivo and in vitro functional analysis

    PMID:22493066 PMID:23247248

    Open questions at the time
    • How SUMOylation modifies Pax7 chromatin interactions not determined
    • Whether Notch-Pax7 axis operates in quiescent vs. activated satellite cells unresolved
  13. 2015 High

    Two proteolytic/degradation mechanisms controlling Pax7 protein turnover were identified: caspase-3 cleaves Pax7 to terminate self-renewal (antagonized by CK2 phosphorylation), and NEDD4 ubiquitin ligase ubiquitinates Pax7 for proteasomal degradation during early differentiation.

    Evidence Caspase-3 cleavage assays; CK2 phosphorylation assays; Nedd4–Pax7 Co-IP; ubiquitination assays; in vivo caspase inhibition

    PMID:26304770 PMID:26372956

    Open questions at the time
    • Specific caspase-3 cleavage site(s) in Pax7 not mapped
    • Whether NEDD4 and caspase-3 act redundantly or sequentially unknown
  14. 2016 High

    CK2 phosphorylation at S201 was pinpointed as a stabilizing modification that protects Pax7 from ubiquitination, mechanistically linking the kinase to protein turnover control in proliferating progenitors.

    Evidence S201A/D point mutations; CK2 inhibitor treatment; ubiquitination assays; proliferation/differentiation assays

    PMID:27144531

    Open questions at the time
    • Whether S201 phosphorylation also affects caspase-3 cleavage directly not tested in this study
    • Upstream signals activating CK2 in satellite cells uncharacterized
  15. 2018 High

    The pioneer mechanism of Pax7 was shown to create stable epigenetic memory: Pax7-opened enhancers lose DNA methylation and remain accessible even after Pax7 withdrawal, explaining how transient Pax7 expression can permanently establish cell identity.

    Evidence ATAC-seq, ChIP-seq, bisulfite sequencing with inducible Pax7 expression and withdrawal in pituitary cells

    PMID:29358650

    Open questions at the time
    • Epigenetic memory mechanism in satellite cells not directly tested
    • Factors maintaining accessibility after Pax7 withdrawal not identified
  16. 2021 High

    Three studies resolved how Pax7 pioneer activity works at the molecular level and how acetylation tunes its target selectivity: both paired and homeodomain are required in cis for opening heterochromatin at composite sites, MYST1-mediated acetylation promotes homeodomain-motif binding, and SIRT2 opposes this to control asymmetric division and stem cell pool size.

    Evidence Point mutations in paired/homeodomain DNA-contact residues with chromatin accessibility assays; in vitro acetylation by MYST1; CRISPR acetylation-site mutant mice; ChIP-seq and RNA-seq; satellite cell division assays

    PMID:34059674 PMID:34197620

    Open questions at the time
    • Structural basis for how both domains cooperate to open nucleosomes unknown
    • How acetylation and arginine methylation are coordinated on the same molecule not addressed
  17. 2021 High

    Pax7 was shown to be synthetically essential with PTEN loss in fusion-negative rhabdomyosarcoma: deleting Pax7 in Pten-null tumors converted them to leiomyosarcoma, demonstrating Pax7 locks tumor cells into a myogenic lineage identity.

    Evidence Mouse genetic model with Pten deletion and Pax7 deletion; tumor histology and gene expression profiling

    PMID:34535684

    Open questions at the time
    • Direct Pax7 chromatin targets maintaining FN-RMS identity not mapped
    • Whether this applies to human FN-RMS tumors not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions remain: the structural basis for Pax7 pioneer nucleosome engagement, how multiple post-translational modifications (methylation, acetylation, phosphorylation, SUMOylation) are integrated on the same molecule in single cells, and whether the epigenetic memory mechanism demonstrated in pituitary melanotropes operates equivalently in satellite cells.
  • No structural model of Pax7–nucleosome complex
  • Coordinated regulation of multiple PTMs on Pax7 not studied
  • Pioneer activity in satellite cells not directly demonstrated at genome scale

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 6
Localization
GO:0005634 nucleus 6
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3
Partners
CARM1FOXO1MEIS2MYST1NEDD4PAX3/7BPSIRT2WDR5
Complex memberships
MLL1/2-ASH2L-WDR5-RBBP5 H3K4 methyltransferase complex (recruited via Pax3/7BP)

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 PAX7 contains a paired box, an octapeptide, and a paired-type homeobox, and is expressed during embryogenesis in the nervous system (brain, dorsal neural tube) and in skeletal muscle from the dermamyotome, establishing its domain architecture and dual CNS/muscle expression. Northern blot and in situ hybridization in mouse embryos Mechanisms of development Medium 1982921
1994 The t(1;13)(p36;q14) chromosomal translocation in alveolar rhabdomyosarcoma fuses the PAX7 paired/homeodomain DNA-binding region (5′) to the FKHR transactivation domain (3′), creating a chimeric transcription factor analogous to PAX3-FKHR. RT-PCR, sequencing of fusion transcript from tumor samples Cancer research High 8187070
1996 The PAX7-FKHR fusion gene can be amplified on double minutes in alveolar rhabdomyosarcoma, arising from insertion of PAX7 sequences into the first intron of FKHR. CGH, FISH, RT-PCR and sequence analysis of tumor samples Genes, chromosomes & cancer Medium 8889501
1996 Pax7-null mice exhibit malformations in facial structures (maxilla, nose) attributable to a cephalic neural crest defect, demonstrating that Pax7 is required for cephalic neural crest-derived tissue development in vivo. Homologous recombination gene knockout in mice; histological and phenotypic analysis Development (Cambridge, England) High 8631261
1999 PAX7 and PAX3 each contain a conserved cis-acting N-terminal repression domain that suppresses their own transactivation activity; PAX7-FKHR gains function because the FKHR transactivation domain is resistant to this cis-repression, resulting in ~600-fold transcriptional activity above background. Deletion analysis, domain swapping, luciferase reporter assays with PAX-specific DNA-binding sites Oncogene High 10439042
1999 Pax7 expression is upregulated and expands into the dorsal neural tube and somites in Pax3-mutant embryos, demonstrating that Pax3 normally represses Pax7 during neural tube and somite development. Analysis of Pax3 mutant (Splotch) mouse embryos; antisense oligonucleotide knockdown of Pax3 in presomitic mesoderm cultures Development (Cambridge, England) Medium 10079229
2004 Pax7 is required for postnatal renewal and maintenance of muscle satellite cells but not their initial specification; satellite cells are progressively lost in Pax7−/− mice during postnatal development and muscle regeneration is impaired. Pax7-null mouse analysis; satellite cell counting, regeneration assays The EMBO journal High 15282552
2004 Pax7 can substitute for Pax3 in dorsal neural tube, neural crest, and somite development when knocked into the Pax3 locus, but cannot support long-range migration of limb muscle progenitors due to defects in delamination, migration, proliferation, and inefficient c-Met activation in the hypaxial somite. Gene targeting (Pax3 locus replaced by Pax7); analysis of muscle formation, c-Met expression, and cell migration Genes & development High 15132998
2005 A Pax3/Pax7-double-positive progenitor cell population constitutes resident muscle progenitors throughout embryonic and fetal development; in the absence of both Pax3 and Pax7, further muscle development after early myotome formation is arrested and cells die or assume non-myogenic fates. GFP reporter targeted to Pax3 locus; Pax3/Pax7 double-mutant mouse analysis; lineage tracing Nature High 15843801
2005 Dominant-negative forms of Pax7 repress MyoD but not Myf5 expression in satellite cells; in Pax7 mutants, satellite cells are progressively lost due to apoptosis with effects on cell cycle, and Pax3 cannot replace the anti-apoptotic function of Pax7. Dominant-negative Pax7 and Pax3 overexpression in satellite cell cultures; Pax7 mutant mouse analysis; apoptosis assays The Journal of cell biology High 16380438
2006 Pax7 is essential for the formation of functional myogenic progenitors from sublaminar satellite cells; Pax7-deficient mice lack functional satellite cells and show severe muscle wasting and regeneration deficit, whereas interstitial Pax3+ cells represent a distinct PAX7-independent myogenic population. Pax7-null mouse (129Sv/J background); single myofiber isolation; immunostaining; muscle regeneration assays The Journal of cell biology High 16391000
2006 Pax7 specifies neural crest cells during gastrulation in chick embryos; blocking Pax7 translation inhibits expression of neural crest markers Slug, Sox9, Sox10, and HNK-1 in vivo. Morpholino antisense knockdown in chick embryos; explant assays; immunostaining for neural crest markers Nature High 16688176
2007 Pax7 prevents muscle differentiation independently of its transcriptional activity by affecting MyoD function; conversely, myogenin directly represses Pax7 expression, establishing a cross-inhibitory interaction between Pax7 and muscle regulatory factors that controls satellite cell fate. Pax7 overexpression in primary myoblasts; analysis of MyoD function; myogenin knockdown/overexpression The Journal of cell biology High 17548510
2007 Myostatin negatively regulates Pax7 expression via ERK1/2 signaling; blocking or inactivating Myostatin enhances Pax7 expression and promotes satellite cell self-renewal, while Pax7 overexpression in C2C12 cells increases self-renewal by slowing proliferation and differentiation. Myostatin treatment and genetic inactivation; ERK1/2 inhibition; Pax7 overexpression assays in C2C12 cells Experimental cell research Medium 17949710
2009 Id3 is a direct transcriptional target of Pax7 in quiescent satellite cells; Pax7 binds upstream of the Id3 promoter (confirmed by ChIP) and activates an Id3-luciferase reporter through a conserved Pax7 binding site, suggesting Pax7 blocks premature differentiation by inducing Id2 and Id3. ChIP in quiescent satellite cells; luciferase reporter assay; Pax7 shRNA knockdown; RT-PCR Molecular biology of the cell High 19458195
2010 miR-206 and miR-486 are induced during myoblast differentiation, directly target the 3′ UTR of Pax7 to downregulate it, and accelerate differentiation; inhibition of these miRNAs causes Pax7 protein persistence and delayed differentiation, and a miRNA-resistant Pax7 is sufficient to inhibit differentiation, forming a bistable switch. miRNA overexpression/inhibition; 3′UTR luciferase reporter assays; Pax7 miRNA-resistant mutant; differentiation assays in myoblasts Molecular and cellular biology High 21041476
2010 TNF-activated p38α kinase phosphorylates EZH2 at threonine 372, promoting interaction between YY1 and the PRC2 complex, leading to formation of repressive chromatin on the Pax7 promoter and repression of Pax7 expression; Pax7 knockdown impairs satellite cell proliferation in response to p38 inhibition. Phosphorylation assays; Co-IP of YY1-PRC2; ChIP on Pax7 promoter; genetic knockdown of p38α and EZH2; in vivo pharmacological inhibition Cell stem cell High 20887952
2012 The arginine methyltransferase Carm1 methylates multiple arginines in the N-terminus of Pax7; methylated Pax7 directly binds C-terminal cleavage forms of MLL1/2, recruiting the ASH2L:MLL1/2:WDR5:RBBP5 H3K4 methyltransferase complex to Myf5 regulatory enhancers and promoter, driving de novo Myf5 transcription during asymmetric satellite stem cell divisions. Co-IP of Carm1-Pax7; in vitro methylation assay; ChIP of MLL1/2 at Myf5 locus; Carm1 knockdown; asymmetric division analysis Cell stem cell High 22863532
2012 Pax3/7BP (a previously uncharacterized nuclear protein) physically interacts with Pax7 and serves as an adaptor bridging Pax7 to Wdr5 to recruit the H3K4 histone methyltransferase complex; knockdown of Pax3/7BP abolishes Pax7-associated H3K4 HMT activity and inhibits proliferation of Pax7+ muscle progenitor cells; Id3 and Cdc20 are direct Pax7/Pax3/7BP target genes. Yeast two-hybrid; Co-IP; H3K4 methyltransferase assay; ChIP; shRNA knockdown in vitro and in vivo Cell stem cell High 22862948
2012 Constitutively active Notch1 (NICD) upregulates Pax7 and promotes self-renewal of satellite cell-derived myoblasts; NICD regulates Pax7 through interaction with RBP-Jκ, which binds two consensus sites upstream of the Pax7 gene, independently of MyoD inhibition. NICD overexpression in myoblasts; MyoD−/− myoblasts; ChIP of RBP-Jκ at Pax7 upstream sites; in vivo satellite cell-specific NICD overexpression Molecular and cellular biology High 22493066
2012 In adult myoblasts, Pax7 binds a far larger fraction of genomic targets than Pax3 (Pax3 occupies only 6.4% of Pax7 targets), and Pax7 has a higher binding affinity to the homeodomain-binding motif relative to Pax3, contributing to its transcriptional dominance in adult myogenesis and regulation of proliferation/differentiation gene panels. Genome-wide ChIP-seq; gene expression profiling; in vitro DNA binding affinity assays Developmental cell High 22609161
2012 Myogenin represses Pax7 transcription in differentiating myoblasts by binding to specific recognition sites in the Pax7 promoter; HMGB1-RAGE signaling is required for myogenin induction and myogenin-dependent Pax7 repression via p38-MAPK activation. Pax7 promoter reporter assays; ChIP of myogenin at Pax7 promoter; RAGE knockout mice; p38 inhibition Journal of cell science High 22328527
2012 Pax7 acts as a pioneer transcription factor in pituitary intermediate lobe cells: it remodels chromatin to allow Tpit binding to a new subset of enhancers for melanotrope-specific gene activation, thereby selecting melanotrope over corticotrope identity; Pax7 inactivation results in loss of melanotrope gene expression and derepression of corticotrope genes. Pax7 gene knockout; genome-wide ChIP analysis; ATAC/chromatin accessibility; gene expression profiling Genes & development High 23070814
2012 PAX7/FOXO1A (from the t(1;13) translocation) suppresses the transcriptional activation of MyoD-target genes (myogenin, muscle creatine kinase) in muscle cells not by blocking MyoD DNA binding but by reducing RNA polymerase II occupancy and histone H4 acetylation at the myogenin promoter. ChIP for MyoD, RNA Pol II, and H4 acetylation at myogenin promoter; luciferase reporter assays; overexpression in satellite cells and C2C12 cells Oncogene High 22710712
2012 SUMOylation of Pax7 at lysine 85 (K85) by the SUMO conjugating enzyme Ubc9 is essential for Pax7 function in neural crest development, C2C12 myogenic differentiation, and transcriptional transactivation; a non-SUMOylatable K85R Pax7 variant is loss-of-function. Co-IP of Pax7-Ubc9; in vivo SUMOylation assay; K85R point mutant analysis in neural crest and myogenic differentiation assays; transcriptional reporter assays Cellular and molecular life sciences High 23247248
2013 NF-κB signaling induces Pax7 overexpression in muscle progenitors in the tumor microenvironment during cancer cachexia; persistent Pax7 prevents myogenic differentiation, and reduction of Pax7 or exogenous MyoD addition reverses wasting by restoring differentiation and fusion with injured fibers. NF-κB inhibition; Pax7 overexpression in normal muscle; Pax7 shRNA knockdown in tumor-bearing mice; serum factor treatment in vitro The Journal of clinical investigation High 24084740
2015 Caspase 3 cleaves and inactivates Pax7 protein, which is required for terminating satellite cell self-renewal and initiating myogenic differentiation; caspase 3 inhibition elevates Pax7 protein and increases self-renewal, while caspase activation leads to Pax7 cleavage and differentiation. CK2-directed phosphorylation of Pax7 attenuates caspase-directed cleavage. Caspase 3 cleavage assay of Pax7; caspase inhibitor treatment; in vivo caspase 3 inhibition; CK2 phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America High 26372956
2015 NEDD4 ubiquitin-ligase physically interacts with Pax7 during early muscle differentiation, promotes Pax7 ubiquitination and proteasomal degradation, and thereby controls the Pax7-to-MyoD ratio to drive differentiation; transient nuclear accumulation of Nedd4 induces a drop in Pax7 levels and precocious muscle differentiation. Co-IP of Nedd4-Pax7; ubiquitination assay; Nedd4 loss-of-function; nuclear targeting experiments; differentiation assays Stem cells (Dayton, Ohio) High 26304770
2015 miR-133b (and to a lesser degree miR-206) are induced by Wnt/β-catenin signaling and directly target the Pax7 3′UTR (at adjacent binding sites) to suppress Pax7 expression and enable myogenic differentiation; miR-133b is a more potent Pax7 inhibitor than miR-206. 3′UTR luciferase reporter assays; β-catenin null primary myoblasts; miRNA overexpression/inhibition; exosome secretion analysis Journal of cellular biochemistry Medium 30945349
2015 Brg1 (SWI/SNF ATPase) directly activates transcription at the Pax7 promoter through chromatin remodeling; Brg1 deletion in satellite cells reduces Pax7 expression, leading to apoptosis and proliferation defects that are rescued by reintroduction of catalytically active Brg1 or Pax7. Brg1 conditional deletion in satellite cells; ChIP at Pax7 promoter; Brg1/Pax7 rescue experiments; proliferation and apoptosis assays Journal of cellular physiology High 26036967
2016 CK2-dependent phosphorylation of Pax7 at serine 201 (S201) maintains Pax7 protein levels in proliferating muscle progenitors; S201 point mutations or CK2 inhibition decrease Pax7 protein, increase Pax7 ubiquitination, and cause precocious myogenic differentiation. S201 point mutation analysis; CK2 inhibitor treatment; ubiquitination assays; proliferation and differentiation assays in myoblasts PloS one High 27144531
2016 Pax7 mediates lineage-specific DNA demethylation at key myogenic loci (including myogenin), an event required for muscle cell identity and differentiation; this demethylation involves the enzyme Apobec2 and is a prerequisite for gene activation in muscle stem cells. Bisulfite sequencing; Pax7-induced ES cell-derived myogenic progenitors; Apobec2 knockdown; differentiation assays BMC biology Medium 27075038
2017 EWSR1-FLI1 fusion protein is required for PAX7 expression in Ewing sarcoma; a candidate EWSR1-FLI1-bound GGAA repeat-containing enhancer upstream of PAX7 coincides with H3K27 acetylation, indicating direct transcriptional activation of PAX7 by the fusion oncoprotein. ChIP-seq and RNA-seq analysis; EWSR1 knockdown; enhancer identification by GGAA repeat analysis and H3K27ac ChIP Modern pathology Medium 28643791
2017 Meis2 physically interacts with Pax7 (and Pax3) in the tectal anlage; Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, and Meis2 expression depends on balanced Pax3/7 levels. Co-IP of Meis2-Pax7; in ovo electroporation in chick embryos; expression analysis BMC developmental biology Medium 22390724
2017 Notch signaling directly regulates Pax7 as a target gene in the embryonic tongue; Pax7 expression in tongue myogenic progenitors is downstream of Notch signaling within a Wnt/Notch/Pax7 genetic hierarchy required for tongue muscle tissue integrity. Conditional Wls deletion in tongue epithelium; genetic epistasis analysis; Notch target gene analysis; in vivo mouse mutants The Journal of biological chemistry Medium 28438836
2018 Pax7 acts as a pioneer transcription factor that is necessary and sufficient for specification of the pituitary melanotrope lineage by opening a unique repertoire of enhancers; Pax7-opened enhancers show loss of DNA methylation and acquire stable epigenetic memory maintained even after Pax7 withdrawal, enabling binding by non-pioneer factors. ATAC-seq; ChIP-seq; bisulfite sequencing; inducible Pax7 expression and withdrawal; genome-wide binding analysis Nature genetics High 29358650
2021 PAX7 is acetylated at two sites by the acetyltransferase MYST1 (stimulated by Acetyl-CoA) and deacetylated by SIRT2 (stimulated by NAD+); acetylation promotes PAX7 DNA binding specifically at homeodomain motifs. Abolishing acetylation by CRISPR/Cas9 in mice leads to expansion of satellite stem cells, reduced asymmetric divisions, increased IIA myofibers, and preferential loss of homeodomain-motif target gene expression. In vitro acetylation assay; CRISPR/Cas9 mutagenesis; ChIP-seq; RNA-seq; satellite cell asymmetric division assays; MYST1/SIRT2 manipulation Nature communications High 34059674
2021 Pax7 pioneer action on chromatin requires both the paired and homeodomain DNA binding domains of the same molecule; composite DNA sites juxtaposing paired and homeodomain targets constitute higher-affinity binding sites and are specifically required for opening heterochromatin; binding to these composite sites is not sensitive to cytosine methylation, consistent with pioneer function. Pax7 single amino acid mutations in paired or homeodomain; in vitro binding affinity assays; chromatin accessibility assays; methylated DNA binding assays Nucleic acids research High 34197620
2021 In fusion-negative rhabdomyosarcoma, Pax7 expression is induced downstream of PTEN loss and is required to maintain tumor identity; Pax7 deletion in Pten-deleted tumors completely rescues the FN-RMS phenotype, instead producing smooth muscle-like leiomyosarcoma, demonstrating synthetic essentiality between PTEN and PAX7 in maintaining tumor cell lineage identity. Mouse genetic model (Pten deletion); Pax7 deletion rescue; tumor histology and gene expression analysis Nature communications High 34535684

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. Nature 841 15843801
2005 Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells. The Journal of cell biology 524 16380438
1994 Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma. Cancer research 516 8187070
2004 Pax7 directs postnatal renewal and propagation of myogenic satellite cells but not their specification. The EMBO journal 382 15282552
2006 Distinct roles for Pax7 and Pax3 in adult regenerative myogenesis. The Journal of cell biology 363 16391000
2010 miR-206 and -486 induce myoblast differentiation by downregulating Pax7. Molecular and cellular biology 344 21041476
2010 TNF/p38α/polycomb signaling to Pax7 locus in satellite cells links inflammation to the epigenetic control of muscle regeneration. Cell stem cell 320 20887952
1990 The murine paired box gene, Pax7, is expressed specifically during the development of the nervous and muscular system. Mechanisms of development 320 1982921
2006 Specification of the neural crest occurs during gastrulation and requires Pax7. Nature 304 16688176
2010 Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells. Genesis (New York, N.Y. : 2000) 302 20641127
2013 NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia. The Journal of clinical investigation 300 24084740
1996 Dysgenesis of cephalic neural crest derivatives in Pax7-/- mutant mice. Development (Cambridge, England) 260 8631261
2004 Divergent functions of murine Pax3 and Pax7 in limb muscle development. Genes & development 240 15132998
2007 Reciprocal inhibition between Pax7 and muscle regulatory factors modulates myogenic cell fate determination. The Journal of cell biology 226 17548510
2012 Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells. Molecular and cellular biology 211 22493066
2004 Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin. Genes & development 196 15520281
2015 PAX3 and PAX7 as upstream regulators of myogenesis. Seminars in cell & developmental biology 182 26424495
2012 Carm1 regulates Pax7 transcriptional activity through MLL1/2 recruitment during asymmetric satellite stem cell divisions. Cell stem cell 174 22863532
1997 Distributions of PAX6 and PAX7 proteins suggest their involvement in both early and late phases of chick brain development. Mechanisms of development 167 9376315
1999 Pax3 functions in cell survival and in pax7 regulation. Development (Cambridge, England) 149 10079229
2014 Derivation and expansion of PAX7-positive muscle progenitors from human and mouse embryonic stem cells. Stem cell reports 145 25241748
2012 Transcriptional dominance of Pax7 in adult myogenesis is due to high-affinity recognition of homeodomain motifs. Developmental cell 143 22609161
2013 Derivation and FACS-mediated purification of PAX3+/PAX7+ skeletal muscle precursors from human pluripotent stem cells. Stem cell reports 133 24371814
2018 Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate. Nature genetics 127 29358650
1998 Pax3 and Pax7 are expressed in commissural neurons and restrict ventral neuronal identity in the spinal cord. Mechanisms of development 119 9858722
2008 Sequential actions of Pax3 and Pax7 drive xanthophore development in zebrafish neural crest. Developmental biology 116 18417109
2018 Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution. Development (Cambridge, England) 115 30305290
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