Dystrophin Dp71 Expression Is Down-regulated during Myogenesis

León, Mario Bermúdez de; Montañéz, Cecilia; Gómez, Pablo; Morales‐Lázaro, Sara L.; Tapia-Ramírez, Victor; Valadéz-Graham, Viviana; Recillas‐Targa, Félix; Yaffe, David; Nudel, Uri; Cisneros, Bulmaro

doi:10.1074/jbc.m411571200

Cited by 40 publications

(27 citation statements)

References 52 publications

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“…In myotubes, MyoD represses the expression of the Sp1 and Sp3 genes, and the resulting scarcity of these transcription factors causes down-regulation of the Dp71 promoter. In early myogenesis, Dp71 is expressed to participate in cytoskeletal remodelling [65]. Thus, the down-regulation of Sp1 suggests a crucial role for GTP in promoting differentiation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profile of GTP-mediated differentiation of C2C12 skeletal muscle cells

Mancinelli

Pietrangelo

Burnstock³

et al. 2011

Purinergic Signalling

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Several purine receptors have been localised on skeletal muscle membranes. Previous data support the hypothesis that extracellular guanosine 5′-triphosphate (GTP) is an important regulatory factor in the development and function of muscle tissue. We have previously described specific extracellular binding sites for GTP on the plasma membrane of mouse skeletal muscle (C2C12) cells. Extracellular GTP induces an increase in intracellular Ca 2+ concentrations that results in membrane hyperpolarisation through Ca 2+ -activated K + channels, as has been demonstrated by patch-clamp experiments. This GTPevoked increase in intracellular Ca 2+ is due to release of Ca 2+ from intracellular inositol-1,4,5-trisphosphate-sensitive stores. This enhances the expression of the myosin heavy chain in these C2C12 myoblasts and commits them to fuse into multinucleated myotubes, probably via a phosphoinositide-3-kinase-dependent signal-transduction mechanism. To define the signalling of extracellular GTP as an enhancer or modulator of myogenesis, we investigated whether the gene-expression profile of differentiated C2C12 cells (4 and 24 h in culture) is affected by extracellular GTP. To investigate the nuclear activity and target genes modulated by GTP, transcriptional profile analysis and realtime PCR were used. We demonstrate that in the early stages of differentiation, GTP up-regulates genes involved in different pathways associated with myogenic processes, including cytoskeleton structure, the respiratory chain, myogenesis, chromatin reorganisation, cell adhesion, and the Jak/Stat pathway, and down-regulates the mitogenactivated protein kinase pathway. GTP also increases the expression of three genes involved in myogenesis, Pp3ca, Gsk3b, and Pax7. Our data suggests that in the myogenic C2C12 cell line, extracellular GTP acts as a differentiative factor in the induction and sustaining of myogenesis.

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Section: Discussionmentioning

confidence: 99%

Transcriptional profile of GTP-mediated differentiation of C2C12 skeletal muscle cells

Mancinelli

Pietrangelo

Burnstock³

et al. 2011

Purinergic Signalling

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“…It was found that a 224-bp proximal promoter region containing four Sp1 binding sites and one activating protein 2 (AP2) element is necessary and sufficient for baseline expression of Dp71 in both muscular and neuronal cells. Furthermore, it was demonstrated that the proximal promoter region controls the repression of Dp71 expression that occurs during myogenesis, as well as promoter activity induction in differentiated neuronal cells [35,36]. In myoblasts, Sp1, together with specificity protein 3 (Sp3), transactivate the Dp71 promoter; however, Sp1 and −3 protein levels decrease during muscle cell differentiation, ultimately causing downregulation of the promoter in mature muscle cells [35] (Fig.…”

Section: Regulation Of Dp71 Expressionmentioning

confidence: 98%

Dystrophin Dp71: The Smallest but Multifunctional Product of the Duchenne Muscular Dystrophy Gene

et al. 2011

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Dystrophin Dp71 is expressed in all tissues, with the exception of skeletal muscle, and is the main Duchenne muscular dystrophy (DMD) gene product in brain. As full-length dystrophin does in skeletal muscle, Dp71 associates with dystroglycans, sarcoglycans, dystrobrevins, syntrophins, and accessory proteins to form the dystrophin-associated protein complex (DAPC) in non-muscle tissues. Although it has been nearly 20 years since the discovery of Dp71, its study has become relevant only recently due to its direct involvement with the two main DMD non-muscular phenotypes: cognitive impairment and abnormal retinal physiology. In this review, we describe the historical background of Dp71 and the experimental models developed for its study. Additionally, we present and discuss the experimental evidence supporting the participation of Dp71 in different cellular processes, including cell adhesion, water homeostasis, cell division, and nuclear architecture. The functional diversity of Dp71 is attributed to the formation of Dp71-containing DAPC in numerous cell types and different subcellular compartments, including in plasma membrane and nucleus, as well as to the capability of Dp71-containing DAPC to work as the scaffold for proper clustering and anchoring of structural and signaling proteins to the plasma membrane and of nuclear envelope proteins to the inner nuclear membrane.

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“…Despite their different transcriptional functions, Sp1 and Sp3, generally compete for the same DNA-binding sites. In situ, several studies have demonstrated that both factors are associated to DNA-binding sites of a variety of promoters (53)(54)(55)(56)(57). They form homotypic and heterotypic complexes with numerous proteins, including other Sp family members (58 -60).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 (IL-6) and/or Soluble IL-6 Receptor Down-regulation of Human Type II Collagen Gene Expression in Articular Chondrocytes Requires a Decrease of Sp1·Sp3 Ratio and of the Binding Activity of Both Factors to the COL2A1 Promoter

Porée

Kypriotou²,

Chadjichristos³

et al. 2008

Journal of Biological Chemistry

131

106

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Type II collagen is composed of ␣1(II) chains encoded by the COL2A1 gene. Alteration of this cartilage marker is a common feature of osteoarthritis. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that needs a soluble form of receptor called sIL-6R to exert its effects in some cellular models. In that case, sIL-6R exerts agonistic action. This mechanism can make up for the partial or total absence of membrane-anchored IL-6 receptors in some cell types, such as chondrocytes. Our study shows that IL-6, sIL-6R, or both inhibit type II collagen production by rabbit articular chondrocytes through a transcriptional control. The cytokine and/or sIL-6R repress COL2A1 transcription by a ؊63/؊35 sequence that binds Sp1⅐Sp3. Indeed, IL-6 and/or sIL-6R inhibit Sp1 and Sp3 expression and their binding activity to the 63-bp promoter. In chromatin immunoprecipitation experiments, IL-6⅐sIL-6R induced an increase in Sp3 recruitment to the detriment of Sp1. Knockdown of Sp1⅐Sp3 by small interference RNA and decoy strategies were found to prevent the IL-6-and/or sIL-6R-induced inhibition of COL2A1 transcription, indicating that each of these Sp proteins is required for down-regulation of the target gene and that a heterotypic Sp1⅐Sp3 complex is involved. Additionally, Sp1 was shown to interact with Sp3 and HDAC1. Indeed, overexpression of a fulllength Sp3 cDNA blocked the Sp1 up-regulation of the 63-bp COL2A1 promoter activity, and by itself, inhibits COL2A1 transcription. We can conclude that IL-6, sIL-6R, or both in combination decrease both the Sp1⅐Sp3 ratio and DNA-binding activities, thus inhibiting COL2A1 transcription. Extracellular matrix (ECM)6 of articular cartilage contains tissue-specific macromolecules including types II, IX, and XI collagens and the large aggregating proteoglycan (PG) aggrecan (1). Type II collagen is the major collagen synthesized by chondrocytes in mature articular cartilage. Each ␣1(II) procollagen chain of the triple helix is encoded by the COL2A1 gene, whose transcription is regulated by DNA elements within both the promoter and the first intron regions (2). Thus, several binding sites of the intronic enhancer were shown to interact with transcription factors such as Sox9, L-Sox5, and Sox6 (3, 4), required for cartilage-specific expression of type II collagen during chondrogenesis in vivo (5), as well as with zinc finger transcription factors Sp1, Sp3, and C-Krox (6, 7). The three latter proteins are also able to bind to several binding sites identified in a 266-bp promoter of the human COL2A1 gene (6 -8). Sp1 was shown to be a strong activator of COL2A1 gene expression via the promoter binding sites, whereas Sp3 was found to prevent the Sp1 up-regulation of the COL2A1 promoter activity by binding to the same cis-acting elements (7).In healthy cartilage, chondrocytes maintain steady-state expression of collagens and PGs and are sensitive to a number of growth factors and cytokines that either enhance or reduce type II collagen synthesis. In osteoarthritis and rheumatoid arthritis, structural...

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Dystrophin Dp71 Expression Is Down-regulated during Myogenesis

Cited by 40 publications

References 52 publications

Transcriptional profile of GTP-mediated differentiation of C2C12 skeletal muscle cells

Transcriptional profile of GTP-mediated differentiation of C2C12 skeletal muscle cells

Dystrophin Dp71: The Smallest but Multifunctional Product of the Duchenne Muscular Dystrophy Gene

Interleukin-6 (IL-6) and/or Soluble IL-6 Receptor Down-regulation of Human Type II Collagen Gene Expression in Articular Chondrocytes Requires a Decrease of Sp1·Sp3 Ratio and of the Binding Activity of Both Factors to the COL2A1 Promoter

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