Author Correction: Identification of MyoD-Responsive Transcripts Reveals a Novel Long Non-coding RNA (lncRNA-AK143003) that Negatively Regulates Myoblast Differentiation.
Ontology highlight
ABSTRACT:
SUBMITTER: Guo Y
PROVIDER: S-EPMC9894926 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
Publications
Author Correction: Identification of MyoD-Responsive Transcripts Reveals a Novel Long Non-coding RNA (lncRNA-AK143003) that Negatively Regulates Myoblast Differentiation.
Guo Yiwen Y Wang Jingnan J Zhu Mingfei M Zeng Rui R Xu Zaiyan Z Li Guoliang G Zuo Bo B
Scientific reports 20230202 1
Similar Datasets
Project description:Myogenic differentiation factor (MyoD) is a master transcription factor in muscle development and differentiation. Although several long non-coding RNAs (lncRNAs) linked to MyoD have been found to influence muscle development, the functions of many lncRNAs have not been explored. Here we utilized lncRNA and mRNA microarray analysis to identify potential lncRNAs regulated by MyoD in muscle cells. A total of 997 differentially expressed lncRNAs (335 up-regulated and 662 down-regulated) and 1,817 differentially expressed mRNAs (148 up-regulated and 1,669 down-regulated) were identified after MyoD knockdown in C2C12 cells. Functional predictions suggested that most lncRNAs are involved in the biological pathways related to muscle differentiation and cell cycle with co-expressed genes. To gain further insight into the MyoD-mediated lncRNA expression in muscle differentiation, tissue expression profiles and MyoD overexpression were performed, and we found one of the candidate lncRNAs-AK143003 was significantly regulated by MyoD. Further analyses showed its noncoding ability and cytoplasmic localisation. Silencing of AK143003 stimulated the accumulation of myogenic marker genes, whereas AK143003 overexpression led to their decreased synthesis. This study identified a multitude of MyoD-mediated lncRNAs for further investigation and identified a novel lncRNA, lnc-AK143003, which plays a role in controlling muscle differentiation.
| S-EPMC5460278 | biostudies-literature
Project description:Abnormal differentiation of muscle is closely associated with aging (sarcopenia) and diseases such as cancer and type II diabetes. Thus, understanding the mechanisms that regulate muscle differentiation will be useful in the treatment and prevention of these conditions. Protein lysine acetylation and methylation are major post-translational modification mechanisms that regulate key cellular processes. In this study, to elucidate the relationship between myogenic differentiation and protein lysine acetylation/methylation, we performed a PCR array of enzymes related to protein lysine acetylation/methylation during C2C12 myoblast differentiation. Our results indicated that the expression pattern of HDAC11 was substantially increased during myoblast differentiation. Furthermore, ectopic expression of HDAC11 completely inhibited myoblast differentiation, concomitant with reduced expression of key myogenic transcription factors. However, the catalytically inactive mutant of HDAC11 (H142/143A) did not impede myoblast differentiation. In addition, wild-type HDAC11, but not the inactive HDAC11 mutant, suppressed MyoD-induced promoter activities of MEF2C and MYOG (Myogenin), and reduced histone acetylation near the E-boxes, the MyoD binding site, of the MEF2C and MYOG promoters. Collectively, our results indicate that HDAC11 would suppress myoblast differentiation via regulation of MyoD-dependent transcription. These findings suggest that HDAC11 is a novel critical target for controlling myoblast differentiation.
| S-EPMC5638774 | biostudies-literature
Project description:Prevention of age-associated reduction in muscle mass and function is required to manage a healthy life. Supplemental (-)-Epicatechin (EC) appears to act as a potential regulator for muscle growth and strength. However, its cellular and molecular mechanisms as a potential muscle growth agent have not been studied well. In the current study, we investigated a role of EC in differentiation of muscle progenitors to gain the molecular insight into how EC regulates muscle growth. EC enhanced myogenic differentiation in a dose-dependent manner through stimulation of promyogenic signaling pathways, p38MAPK and Akt. EC treatment elevated MyoD activity by enhancing its heterodimerization with E protein. Consistently, EC also positively regulated myogenic conversion and differentiation of fibroblasts. In conclusion, EC has a potential as a therapeutic or nutraceutical remedy to treat degenerative muscle diseases or age-related muscle weakness.
| S-EPMC5383328 | biostudies-literature
Project description:E3 ubiquitin ligases are closely related to cell division, differentiation, and survival in all eukaryotes and play crucial regulatory roles in multiple biological processes and diseases. While Deltex2, as a member of the DELTEX family ubiquitin ligases, is characterized by a RING domain followed by a C-terminal domain (DTC), its functions and underlying mechanisms in myogenesis have not been fully elucidated. Here, we report that Deltex2, which is highly expressed in muscles, positively regulates myoblast proliferation via mediating the expression of Pax7. Meanwhile, we find that Deltex2 is translocated from the nucleus into the cytoplasm during myogenic differentiation, and further disclose that Deltex2 inhibits myoblast differentiation and interacts with MyoD, resulting in the ubiquitination and degradation of MyoD. Altogether, our findings reveal the physiological function of Deltex2 in orchestrating myogenesis and delineate the novel role of Deltex2 as a negative regulator of MyoD protein stability.
| S-EPMC10157619 | biostudies-literature
Project description:Skeletal muscle differentiation can be regulated by various transcription factors and non-coding RNAs. In our previous work, miR-223 is differentially expressed in the skeletal muscle of chicken with different growth rates, but its role, expression and action mechanism in muscle development still remains unknown. Here, we found that MYOD transcription factor can upregulate miR-223 expression by binding to an E-box region of the gga-miR-223 gene promoter during avian myoblast differentiation. IGF2 and ZEB1 are two target genes of miR-223. The target inhibition of miR-223 on IGF2 and ZEB1 are dynamic from proliferation to differentiation of myoblast. miR-223 inhibits IGF2 expression only in the proliferating myoblast, whereas it inhibits ZEB1 mainly in the differentiating myoblast. The inhibition of IGF2 by miR-223 resulted in the repression of myoblast proliferation. During myoblast differentiation, miR-223 would be upregulated owing to the promoting effect of MYOD, and the upregulation of miR-223 would inhibit ZEB1 to promote myoblast differentiation. These results not only demonstrated that the well-known muscle determination factor MYOD can promote myoblast differentiation by upregulate miR-223 transcription, but also identified that miR-223 can influence myoblast proliferation and differentiation by a dynamic manner regulates the expression of its target genes.
| S-EPMC5682648 | biostudies-literature
Project description:The presence of tetraplex structures in the promoter region of the myogenic differentiation 1 gene (MyoD1) was investigated with a specific tetraplex-binding porphyrin (TMPyP4), to test its influence on the expression of MyoD1 itself and downstream-regulated genes during myogenic differentiation. TMPyP4-exposed C2C12 myoblasts, blocking MyoD1 transcription, proliferated reaching confluence and fused forming elongated structures, resembling myotubes, devoid of myosin heavy chain 3 (MHC) expression. Besides lack of MHC, upon MyoD1 inhibition, other myogenic gene expressions were also affected in treated cells, while untreated control cell culture showed normal myotube formation expressing MyoD1, Myog, MRF4, Myf5, and MHC. Unexpectedly, the myomaker (Mymk) gene expression was not affected upon TMPyP4 exposure during C2C12 myogenic differentiation. At the genomic level, the bioinformatic comparison of putative tetraplex sites found that three tetraplexes in MyoD1 and Myog are highly conserved in mammals, while Mymk and MHC did not show any conserved tetraplexes in the analysed regions. Thus, here, we report for the first time that the inhibition of the MyoD1 promoter function, stabilizing the tetraplex region, affects downstream myogenic genes by blocking their expression, while leaving the expression of Mymk unaltered. These results reveal the existence of two distinct pathways: one leading to cell fusion and one guaranteeing correct myotube differentiation.
| S-EPMC5964432 | biostudies-literature
Project description:Myostatin, a member of the transforming growth factor-? superfamily, has been implicated in the potent negative regulation of myogenesis in murine models. However, little is known about the mechanism(s) through which human myostatin negatively regulates human skeletal muscle growth. Using human primary myoblasts and recombinant human myostatin protein, we show here that myostatin blocks human myoblast proliferation by regulating cell cycle progression through targeted upregulation of p21. We further show that myostatin regulates myogenic differentiation through the inhibition of key myogenic regulatory factors including MyoD, via canonical Smad signaling. In addition, we have for the first time demonstrated the capability of myostatin to regulate the Notch signaling pathway during inhibition of human myoblast differentiation. Treatment with myostatin results in the upregulation of Hes1, Hes5, and Hey1 expression during differentiation; moreover, when we interfere with Notch signaling, through treatment with the ?-secretase inhibitor L-685,458, we find enhanced myotube formation despite the presence of excess myostatin. Therefore, blockade of the Notch pathway relieves myostatin repression of differentiation, and myostatin upregulates Notch downstream target genes. Immunoprecipitation studies demonstrate that myostatin treatment of myoblasts results in enhanced association of Notch1-intracellular domain with Smad3, providing an additional mechanism through which myostatin targets and represses the activity of the myogenic regulatory factor MyoD. On the basis of these results, we suggest that myostatin function and mechanism of action are very well conserved between species, and that myostatin regulation of postnatal myogenesis involves interactions with numerous downstream signaling mediators, including the Notch pathway.
| S-EPMC3129832 | biostudies-other
Project description:p204, an interferon-inducible p200 family protein, inhibits rRNA synthesis in fibroblasts by blocking the binding of the upstream binding factor transcription factor to DNA. Here we report that among 10 adult mouse tissues tested, the level of p204 was highest in heart and skeletal muscles. In cultured C2C12 skeletal muscle myoblasts, p204 was nucleoplasmic and its level was low. During myoblast fusion this level strongly increased, p204 became phosphorylated, and the bulk of p204 appeared in the cytoplasm of the myotubes. Leptomycin B, an inhibitor of nuclear export that blocked myoblast fusion, inhibited the nuclear export signal-dependent translocation of p204 to the cytoplasm. The increase in the p204 level during myoblast fusion was a consequence of MyoD transcription factor binding to several MyoD-specific sequences in the gene encoding p204, followed by transcription. Overexpression of p204 (in C2C12 myoblasts carrying an inducible p204 expression plasmid) accelerated the fusion of myoblasts to myotubes in differentiation medium and induced the fusion even in growth medium. The level of p204 in mouse heart muscle strongly increased during differentiation; it was barely detectable in 10. 5-day-old embryos, reached the peak level in 16.5-day-old embryos, and remained high thereafter. p204 is the second p200 family protein (after p202a) found to be involved in muscle differentiation. (p202a was formerly designated p202. The new designation is due to the identification of a highly similar protein-p202b [H. Wang, G. Chatterjee, J. J. Meyer, C. J. Liu, N. A. Manjunath, P. Bray-Ward, and P. Lengyel, Genomics 60:281-294, 1999].) These results reveal that p204 and p202a function in both muscle differentiation and interferon action.
| S-EPMC88777 | biostudies-literature
Project description:When mouse myoblasts or satellite cells differentiate in culture, the expression of myogenic regulatory factor, MyoD, is downregulated in a subset of cells that do not differentiate. The mechanism involved in the repression of MyoD expression remains largely unknown. Here we report that a stress-response pathway repressing MyoD transcription is transiently activated in mouse-derived C2C12 myoblasts growing under differentiation-promoting conditions. We show that phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α) is followed by expression of C/EBP homology protein (CHOP) in some myoblasts. ShRNA-driven knockdown of CHOP expression caused earlier and more robust differentiation, whereas its constitutive expression delayed differentiation relative to wild type myoblasts. Cells expressing CHOP did not express the myogenic regulatory factors MyoD and myogenin. These results indicated that CHOP directly repressed the transcription of the MyoD gene. In support of this view, CHOP associated with upstream regulatory region of the MyoD gene and its activity reduced histone acetylation at the enhancer region of MyoD. CHOP interacted with histone deacetylase 1 (HDAC1) in cells. This protein complex may reduce histone acetylation when bound to MyoD regulatory regions. Overall, our results suggest that the activation of a stress pathway in myoblasts transiently downregulate the myogenic program.
| S-EPMC3248460 | biostudies-literature
Project description:Although FoxO and Pax proteins represent two important families of transcription factors in determining cell fate, they had not been functionally or physically linked together in mediating regulation of a common target gene during normal cellular transcription programs. Here, we identify MyoD, a key regulator of myogenesis, as a direct target of FoxO3 and Pax3/7 in myoblasts. Our cell-based assays and in vitro studies reveal a tight codependent partnership between FoxO3 and Pax3/7 to coordinately recruit RNA polymerase II and form a preinitiation complex (PIC) to activate MyoD transcription in myoblasts. The role of FoxO3 in regulating muscle differentiation is confirmed in vivo by observed defects in muscle regeneration caused by MyoD downregulation in FoxO3 null mice. These data establish a mutual interdependence and functional link between two families of transcription activators serving as potential signaling sensors and regulators of cell fate commitment in directing tissue specific MyoD transcription.
| S-EPMC2614327 | biostudies-literature