TLE4 regulates muscle stem cell quiescence and skeletal muscle differentiation

Agarwal, Megha; Bharadwaj, Anushree; Mathew, Sam J.

doi:10.1242/jcs.256008

Cited by 13 publications

(15 citation statements)

References 42 publications

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“…Functional annotation within KEGG pathways showed that it is involved in Wnt and Notch signaling pathways. As a prominent regulator of the canonical Wnt signaling pathway (GO: 0016055) and cellular biosynthetic process (GO: 0031326), TLE4 was recently suggested to regulate muscle satellite cell quiescence and muscle differentiation by repressing PAX7-mediated MYF5 transcriptional activation in mice [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Parameters and Genomic Regions Underlying Growth and Linear Type Traits in Akkaraman Sheep

Kızılaslan

Arzık

White

et al. 2022

Genes

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In the current study, the genetic architecture of growth and linear type traits were investigated in Akkaraman sheep. Estimations of genomic heritability, genetic correlations, and phenotypic correlations were implemented for 17 growth and linear type traits of 473 Akkaraman lambs by the univariate and multivariate analysis of animal mixed models. Correspondingly, moderate heritability estimates, as well as high and positive genetic/phenotypic correlations were found between growth and type traits. On the other hand, 2 genome-wide and 19 chromosome-wide significant single nucleotide polymorphisms were found to be associated with the traits as a result of animal mixed model-based genome-wide association analyses. Accordingly, we propose several genes located on different chromosomes (e.g., PRDM2, PTGDR, PTPRG, KCND2, ZNF260, CPE, GRID2, SCD5, SPIDR, ZNF407, HCN3, TMEM50A, FKBP1A, TLE4, SP1, SLC44A1, and MYOM3) as putative quantitative trait loci for the 22 growth and linear type traits studied. In our study, specific genes (e.g., TLE4, PTGDR, and SCD5) were found common between the traits studied, suggesting an interplay between the genetic backgrounds of these traits. The fact that four of the proposed genes (TLE4, MYOM3, SLC44A1, and TMEM50A) are located on sheep chromosome 2 confirms the importance of these genomic regions for growth and morphological structure in sheep. The results of our study are therefore of great importance for the development of efficient selection indices and marker-assisted selection programs, as well as for the understanding of the genetic architecture of growth and linear traits in sheep.

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Section: Discussionmentioning

confidence: 99%

Genetic Parameters and Genomic Regions Underlying Growth and Linear Type Traits in Akkaraman Sheep

Kızılaslan

Arzık

White

et al. 2022

Genes

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“…TLE4 supresses Pax7-mediated Myf5 transcriptional activation through inducing Myf5 enhancer to continue latency. Loss of TLE4 function results into Myf5 upregulation thus, showing its role in growth through transcription suppression 29 . TLE4 is also a critical regulator in haematopoiesis 30 and bone development 31 .…”

Section: Discussionmentioning

confidence: 99%

Genome wide association study identifies novel candidate genes for growth and body conformation traits in goats

Moaeen‐ud‐Din

Muner²,

Khan³

2022

Sci Rep

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Pakistan is third largest country in term of goat population with distinct characteristics of breeds and estimated population of 78.2 million. Punjab province has 37% of country’s total population with seven important documented goat breeds namely Beetal, Daira Din Pannah, Nachi, Barbari, Teddi, Pahari and Pothwari. There is paucity of literature on GWAS for economically important traits i.e., body weight and morphometric measurements. Therefore, we performed GWAS using 50 K SNP Chip for growth in term of age adjusted body weight and morphometric measurements in order to identify genomic regions influencing these traits among Punjab goat breeds. Blood samples were collected from 879 unrelated animals of seven goat breeds along with data for body weight and morphometric measurements including body length, body height, pubic bone length, heart girth and chest length. Genomic DNA was extracted and genotyped using 50 K SNP bead chip. Association of genotypic data with the phenotypic data was performed using Plink 1.9 software. Linear mixed model was used for the association study. Genes were annotated from Capra hircus genome using assembly ARS1. We have identified a number of highly significant SNPs and respective candidate genes associated with growth and body conformation traits. The functional aspects of these candidate genes suggested their potential role in body growth. Moreover, pleiotropic effects were observed for some SNPs for body weight and conformation traits. The results of current study contributed to a better understanding of genes influencing growth and body conformation traits in goat.

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“…10 TLEs have been shown to play important roles in myogenesis. 11,15 Numerous studies suggest that TLEs interact with homeodomain proteins to repress target genes. 10 Since Zeb1 is a homeodomain protein, we hypothesized that it may interact with TLEs.…”

Section: Zeb1 Inhibits Myhc-embryonic Expression and Muscle Different...mentioning

confidence: 99%

“…Transducin‐like Enhancer of Split (TLE) proteins are a family of corepressors with vital functions during embryonic development, adult homeostasis and regeneration 10 . Recently, we found that Tle4 prevents Pax7‐mediated activation of myogenic factor 5 ( Myf5 ) in quiescent muscle stem cells 11 . Tle3 has been shown to be important in promoting white adipose tissue and mitochondrial gene expression 12–14 .…”

Section: Introductionmentioning

confidence: 99%

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Zeb1 and Tle3 aretrans‐factors that differentially regulate the expression of myosin heavy chain‐embryonic and skeletal muscle differentiation

Kumar,

Zehra,

Saini

et al. 2023

The FASEB Journal

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Myosin heavy chain‐embryonic encoded by the Myh3 gene is a skeletal muscle‐specific contractile protein expressed during mammalian development and regeneration, essential for proper myogenic differentiation and function. It is likely that multiple trans‐factors are involved in this precise temporal regulation of Myh3 expression. We identify a 4230 bp promoter‐enhancer region that drives Myh3 transcription in vitro during C2C12 myogenic differentiation and in vivo during muscle regeneration, including sequences both upstream and downstream of the Myh3 TATA‐box that are necessary for complete Myh3 promoter activity. Using C2C12 mouse myogenic cells, we find that Zinc‐finger E‐box binding homeobox 1 (Zeb1) and Transducin‐like Enhancer of Split 3 (Tle3) proteins are crucial trans‐factors that interact and differentially regulate Myh3 expression. Loss of Zeb1 function results in earlier expression of myogenic differentiation genes and accelerated differentiation, whereas Tle3 depletion leads to reduced expression of myogenic differentiation genes and impaired differentiation. Tle3 knockdown resulted in downregulation of Zeb1, which could be mediated by increased expression of miR‐200c, a microRNA that binds to Zeb1 transcript and degrades it. Tle3 functions upstream of Zeb1 in regulating myogenic differentiation since double knockdown of Zeb1 and Tle3 resulted in effects seen upon Tle3 depletion. We identify a novel E‐box in the Myh3 distal promoter‐enhancer region, where Zeb1 binds to repress Myh3 expression. In addition to regulation of myogenic differentiation at the transcriptional level, we uncover post‐transcriptional regulation by Tle3 to regulate MyoG expression, mediated by the mRNA stabilizing Human antigen R (HuR) protein. Thus, Tle3 and Zeb1 are essential trans‐factors that differentially regulate Myh3 expression and C2C12 cell myogenic differentiation in vitro.

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TLE4 regulates muscle stem cell quiescence and skeletal muscle differentiation

Cited by 13 publications

References 42 publications

Genetic Parameters and Genomic Regions Underlying Growth and Linear Type Traits in Akkaraman Sheep

Genetic Parameters and Genomic Regions Underlying Growth and Linear Type Traits in Akkaraman Sheep

Genome wide association study identifies novel candidate genes for growth and body conformation traits in goats

Zeb1 and Tle3 aretrans‐factors that differentially regulate the expression of myosin heavy chain‐embryonic and skeletal muscle differentiation

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