Overexpression of DNMT3A promotes proliferation and inhibits differentiation of porcine intramuscular preadipocytes by methylating p21 and PPARg promoters

Qimuge, Naren; He, Zhaozhao; Qin, Jin; Sun, Yunmei; Wang, Xiangming; Yu, Taiyong; Dong, Wuzi; Yang, Gongshe; Pang, Wei

doi:10.1016/j.gene.2019.02.029

Cited by 19 publications

(13 citation statements)

References 30 publications

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“…GADD45α is a vital mediator in gene-specific activated DNA demethylation during adult stem cell differentiation and white adipogenesis 24 , 56 . Newly emerging evidence indicates that DNA demethylation plays an important role in regulating PPARγ expression and adipogenesis in intramuscular preadipocytes and 3T3-L1 cells 57 , 58 . GADD45α could recruit demethylation proteins to CpG island promoters 59 , and the CpG demethylation of the PPARγ promoter may contribute to its expression 58 .…”

Section: Discussionmentioning

confidence: 99%

GADD45α drives brown adipose tissue formation through upregulating PPARγ in mice

Sun

Valencak

et al. 2020

Cell Death Dis

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Stress can lead to obesity and metabolic dysfunction, but the underlying mechanisms are unclear. Here we identify GADD45α, a stress-inducible histone folding protein, as a potential regulator for brown adipose tissue biogenesis. Unbiased transcriptomics data indicate a positive correlation between adipose Gadd45a mRNA level and obesity. At the cellular level, Gadd45a knockdown promoted proliferation and lipolysis of brown adipocytes, while Gadd45a overexpression had the opposite effects. Consistently, using a knockout (Gadd45a−/−) mouse line, we found that GADD45α deficiency inhibited lipid accumulation and promoted expression of thermogenic genes in brown adipocytes, leading to improvements in insulin sensitivity, glucose uptake, energy expenditure. At the molecular level, GADD45α deficiency increased proliferation through upregulating expression of cell cycle related genes. GADD45α promoted brown adipogenesis via interacting with PPARγ and upregulating its transcriptional activity. Our new data suggest that GADD45α may be targeted to promote non-shivering thermogenesis and metabolism while counteracting obesity.

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Section: Discussionmentioning

confidence: 99%

GADD45α drives brown adipose tissue formation through upregulating PPARγ in mice

Sun

Valencak

et al. 2020

Cell Death Dis

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“…Growing number of studies suggested that DNA methylation played significantly role in adipogenesis (Broholm et al, 2016;Chen et al, 2016;Lim et al, 2016). Previous studies recommended that DNMT3A inhibited porcine intramuscular preadipocytes differentiation by changing the methylation levels of p21 and PPARγ (Abdalla et al, 2018;Qimuge et al, 2019). Zhang et al (2014) found that MBD4 inhibited porcine preadipocytes differentiation by changing the DNA methylation levels of adipogenic genes.…”

Section: Introductionmentioning

confidence: 99%

The Landscape of DNA Methylation Associated With the Transcriptomic Network of Intramuscular Adipocytes Generates Insight Into Intramuscular Fat Deposition in Chicken

Zhang

Zhai

et al. 2020

Front. Cell Dev. Biol.

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Intramuscular fat (IMF), which regulated by genetics, nutrition and environment is an important factor that influencing meat quality. Up to now, the epigenetic regulation mechanism underlying poultry IMF deposition remains poorly understood. Here, we focused on the DNA methylation, which usually regulate genes in transcription level. To look into the essential role of DNA methylation on the IMF deposition, chicken intramuscular preadipocytes were isolated and cultured in vitro, and a model of intramuscular adipocyte differentiation was constructed. Combined the whole genome bisulfite sequencing (WGBS) and RNA-Seq technologies, we identified several methylated genes, which mainly affecting fatty acid metabolism and muscle development. Furthermore, we reported that DNA methylation regulate intramuscular adipogenesis by regulating the genes, such as collagen, type VI, alpha 1 (COL6A1) thus affecting IMF deposition. Overexpression of COL6A1 increases the lipid droplet and inhibits cell proliferation by regulating CHAD and CAMK2 in intramuscular adipocytes, while knockdown of COL6A1 shows the opposite effect. Taken together, our results reveal that DNA methylation plays an important role in poultry IMF deposition.

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“…Transcriptome analysis has deepened our scientific knowledge of the molecular pathways and genetic basis of fat metabolism and IMF accretion in pigs [ 12 , 94 , 119 ]. To this end, there is clear evidence that the use of nutrient-gene biomarkers is a crucial fingerprint for accurately elucidating the genetic and nutritional regulation of fat metabolism.…”

Section: Qtl Regions and Snps For Fat Metabolism And Imf Accretion In Pigsmentioning

confidence: 99%

“…Many genes regulated by differentially methylated promoters were implicated in lipid metabolism, sensory and olfactory processes, and ATPase activity [ 32 ]. In addition, polygenic trait effects related to IMF deposition and fat metabolism as well as their degree of heritability are controlled/regulated by epigenetic modifications [ 119 , 126 ]. The role of epigenetics in fat metabolism is becoming clearer as studies are uncovering the underlying pattern of expression of coding and non-coding genes as well as the functional role(s) of mRNA and miRNA during adipocyte and myocyte cell differentiation [ 125 ].…”

Section: Epigenetic Mechanisms: Role Of Mrnas Mirnas Dna Methylation and Histone Modification In Fat Metabolismmentioning

confidence: 99%

“…Studies have shown that methylating dietary micronutrients elicited differential expressions of genes involved in lipid metabolism, and later, gene repression of certain housekeeping genes [ 23 ]. Qimuge and others [ 119 ] demonstrated that DNMT3A increased proliferation and inhibited the differentiation of intramuscular preadipocytes by decreasing the expression of cyclin-dependent kinase inhibitor 1A ( p21 also known as CDKN1A ), and down-regulated the levels of PPARγ , SREBP-1c , and FABP4 through the methylation of PPARγ promoter [ 119 ]. The study of Stachecka et al [ 153 ] showed that the onset of adipogenesis elicited an increase in transcript level of DNMT1 gene followed by a decrease, while DNMT3A and DNMT3B gene transcripts increase during the in vitro differentiation.…”

Section: Epigenetic Mechanisms: Role Of Mrnas Mirnas Dna Methylation and Histone Modification In Fat Metabolismmentioning

confidence: 99%

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Genes Related to Fat Metabolism in Pigs and Intramuscular Fat Content of Pork: A Focus on Nutrigenetics and Nutrigenomics

Malgwi

Halas

Grünvald

et al. 2022

Animals

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Fat metabolism and intramuscular fat (IMF) are qualitative traits in pigs whose development are influenced by several genes and metabolic pathways. Nutrigenetics and nutrigenomics offer prospects in estimating nutrients required by a pig. Application of these emerging fields in nutritional science provides an opportunity for matching nutrients based on the genetic make-up of the pig for trait improvements. Today, integration of high throughput “omics” technologies into nutritional genomic research has revealed many quantitative trait loci (QTLs) and single nucleotide polymorphisms (SNPs) for the mutation(s) of key genes directly or indirectly involved in fat metabolism and IMF deposition in pigs. Nutrient–gene interaction and the underlying molecular mechanisms involved in fatty acid synthesis and marbling in pigs is difficult to unravel. While existing knowledge on QTLs and SNPs of genes related to fat metabolism and IMF development is yet to be harmonized, the scientific explanations behind the nature of the existing correlation between the nutrients, the genes and the environment remain unclear, being inconclusive or lacking precision. This paper aimed to: (1) discuss nutrigenetics, nutrigenomics and epigenetic mechanisms controlling fat metabolism and IMF accretion in pigs; (2) highlight the potentials of these concepts in pig nutritional programming and research.

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Overexpression of DNMT3A promotes proliferation and inhibits differentiation of porcine intramuscular preadipocytes by methylating p21 and PPARg promoters

Cited by 19 publications

References 30 publications

GADD45α drives brown adipose tissue formation through upregulating PPARγ in mice

GADD45α drives brown adipose tissue formation through upregulating PPARγ in mice

The Landscape of DNA Methylation Associated With the Transcriptomic Network of Intramuscular Adipocytes Generates Insight Into Intramuscular Fat Deposition in Chicken

Genes Related to Fat Metabolism in Pigs and Intramuscular Fat Content of Pork: A Focus on Nutrigenetics and Nutrigenomics

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