Pax3/7BP Is a Pax7- and Pax3-Binding Protein that Regulates the Proliferation of Muscle Precursor Cells by an Epigenetic Mechanism

Diao, Yarui; Guo, Xing; Li, Yanfeng; Sun, Kun; Lu, Leina; Jiang, Lei; Fu, Xinrong; Zhu, Han; Sun, Hao; Wang, Huating; Wu, Zhenguo

doi:10.1016/j.stem.2012.05.022

Cited by 86 publications

(86 citation statements)

References 45 publications

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“…In vivo , this complex is likely to include additional factors that may vary with context. Candidates include the previously identified Pax3/7 binding protein, Pax3/7BP which recruits an H3K4 histone methyltransferase to target gene promoters (Diao et al, 2012). Taz has been shown to interact with the histone acetyl transferases PCAF and p300 (Murakami et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The trans-activation potential of Pax factors may be modulated by interacting proteins. For example, a Pax3/Pax7 binding protein, Pax3/7BP, can recruit H3K4 histone methyltransferase activity to Pax target genes in C2C12 myoblasts, thus regulating cell proliferation and the expression of the Pax target genes Id3 and Cdc20 (Diao et al, 2012). Pax6 can interact with homeodomain-interacting protein kinase 2 (Hipk2).…”

Section: Introductionmentioning

confidence: 99%

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Pax3 and Hippo Signaling Coordinate Melanocyte Gene Expression in Neural Crest

et al. 2014

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SUMMARY Loss of Pax3, a developmentally regulated transcription factor expressed in pre-migratory neural crest, results in severe developmental defects and embryonic lethality. Although Pax3 mutations produce profound phenotypes, the intrinsic transcriptional activation exhibited by Pax3 is surprisingly modest. We postulated the existence of transcriptional co-activators that function with Pax3 to mediate developmental functions. A high-throughput screen identified the Hippo effector proteins Taz and Yap65 as Pax3 co-activators. Synergistic co-activation of target genes by Pax3-Taz/Yap65 requires DNA binding by Pax3, is Tead-independent, and is regulated by Hippo kinases Mst1 and Lats2. In vivo, Pax3 and Yap65 co-localize in the nucleus of neural crest progenitors in the dorsal neural tube. Neural crest deletion of Taz and Yap65 results in embryonic lethal neural crest defects and decreased expression of the Pax3 target gene, Mitf. These results suggest that Pax3 activity is regulated by the Hippo pathway and that Pax factors are Hippo effectors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pax3 and Hippo Signaling Coordinate Melanocyte Gene Expression in Neural Crest

et al. 2014

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“…In satellite cells, lymphoid progenitors and HEK 293 cells, PAX7, PAX5 and PAX2, respectively, have been shown to recruit histone methyltransferase complexes to the promoter regions (Patel et al, 2007) of genes such as Myf5 and Myod1 , where the PAX transactivation domain links to methyltransferase complexes by an interacting protein (Cho et al, 2003;Fang et al, 2009;Diao et al, 2012). Epigenetic repressive imprints have also been shown to be initiated by PAX proteins through the recruitment of groucho-related gene product 4 (GRG4) to specify a region of chromatin for silencing; in melanoblasts, lymphoid progenitors and HEK 293 cells, PAXmediated gene repression is associated with the recruitment of GRG4, with both proteins interacting cooperatively for resultant transcriptional repression (Eberhard et al, 2000;Lang et al, 2005;Patel et al, 2013).…”

Section: Aberrant Pax Gene Expression: Implications For Regeneration mentioning

confidence: 99%

Pax genes: regulators of lineage specification and progenitor cell maintenance

2014

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Pax genes encode a family of transcription factors that orchestrate complex processes of lineage determination in the developing embryo. Their key role is to specify and maintain progenitor cells through use of complex molecular mechanisms such as alternate RNA splice forms and gene activation or inhibition in conjunction with protein co-factors. The significance of Pax genes in development is highlighted by abnormalities that arise from the expression of mutant Pax genes. Here, we review the molecular functions of Pax genes during development and detail the regulatory mechanisms by which they specify and maintain progenitor cells across various tissue lineages. We also discuss mechanistic insights into the roles of Pax genes in regeneration and in adult diseases, including cancer. KEY WORDS: Pax genes, Embryogenesis, Lineage determination IntroductionPaired box (Pax) genes encode transcription factors that contain a highly conserved DNA-binding domain called the paired domain (PD, Fig. 1A) and can be considered to be a principle regulator of gene expression. Nine Pax genes (Pax1-Pax9) have been characterised in mammals and the evolutionary conserved paired domain has been identified across phylogenies from insects, to amphibians and birds. In higher vertebrates, PAX proteins are subclassified into groups according to inclusion of an additional DNA-binding homeodomain and/or an octapeptide region, which serves as a binding motif for protein co-factors for potent inhibition of downstream gene transcription (Eberhard et al., 2000) (Fig. 1B); all PAX proteins include a transactivation domain located within the C-terminal amino acids (Underhill, 2012). It is also known that all Pax genes, with the exception of Pax4 and Pax9, produce alternative RNA transcripts (see Table 1). The functional diversity of Pax proteins in vivo is thus linked to the ability to produce alternatively spliced gene products that differ in structure and, consequently, in the binding activity of their paired and homeodomain DNA-binding regions (Underhill, 2012).Three decades ago, the characterisation and roles of Pax genes in embryonic development began to unfold. Early studies discovered that regulatory gene families such as the Pax family are involved in the sequential compartmentalisation and body patterning of developing organisms; thereafter, studies highlighted a role for Pax genes in the early specification of cell fate and the subsequent morphogenesis of various tissues and organs. Following this, mutational studies of Pax genes confirmed the importance of these regulatory roles in the PRIMER School of Medical Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.*Author for correspondence (j.blake@ecu.edu.au) This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.initiation and progression of ...

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“…Cell Proliferation Assays-The cell proliferation assays (WST-1 and BrdU labeling experiments) were performed as described previously (47). Briefly, the Premix WST-1 cell proliferation assay system (TaKaRa Bio Inc., Otsu, Japan) was used to examine cell proliferation.…”

Section: Quantitative Rt-pcr (Rt-qpcr)-totalmentioning

confidence: 99%

miR-203, a Tumor Suppressor Frequently Down-regulated by Promoter Hypermethylation in Rhabdomyosarcoma

Diao

Guo

Jiang

et al. 2014

Journal of Biological Chemistry

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Background: Rhabdomyosarcoma (RMS) is a pediatric tumor that expresses several muscle-specific proteins with poor terminal differentiation. Results: miR-203 was frequently down-regulated in RMS, and its re-expression in RMS cells inhibited their growth and migration and promoted terminal differentiation. Conclusion: miR-203 is a tumor suppressor down-regulated in RMS. Significance: miR-203 can serve as a potential target for therapeutic treatment of RMS.

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Pax3/7BP Is a Pax7- and Pax3-Binding Protein that Regulates the Proliferation of Muscle Precursor Cells by an Epigenetic Mechanism

Cited by 86 publications

References 45 publications

Pax3 and Hippo Signaling Coordinate Melanocyte Gene Expression in Neural Crest

Pax3 and Hippo Signaling Coordinate Melanocyte Gene Expression in Neural Crest

Pax genes: regulators of lineage specification and progenitor cell maintenance

miR-203, a Tumor Suppressor Frequently Down-regulated by Promoter Hypermethylation in Rhabdomyosarcoma

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