Investigation of allele-specific expression of genes involved in adipogenesis and lipid metabolism suggests complex regulatory mechanisms of PPARGC1A expression in porcine fat tissues

Stachowiak, Monika; Szczerbal, Izabela; Flisikowski, Krzysztof

doi:10.1186/s12863-018-0696-6

Cited by 10 publications

(9 citation statements)

References 46 publications

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“…The PPARG gene undergoes biallelic expression. Analysis of the allele-specific expression of this gene in porcine fat tissues has shown that both alleles are expressed at similar levels (Stachowiak et al 2018). However, the use of RNA/DNA-FISH allowed us to detect temporal differences in PPARG transcript production.…”

Section: Discussionmentioning

confidence: 99%

The importance of the nuclear positioning of the PPARG gene for its expression during porcine in vitro adipogenesis

et al. 2019

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Proper expression of the PPARG gene, which encodes a key transcription factor of adipogenesis, is indispensable in the formation of mature adipocytes. The positioning of a gene within the nuclear space has been implicated in gene regulation. We here report on the significance of the PPARG gene’s nuclear positioning for its activity during in vitro adipogenesis in the pig. We used an established system of differentiation of mesenchymal stem cells derived from bone marrow and adipose tissue into adipocytes. The differentiation process was carried out for 7 days, and the cells were examined using the 3D DNA/immuno-FISH and RNA/DNA-FISH approaches. PPARG transcript level was measured using real-time PCR, and PPARγ activity was detected with colorimetric assay. Changes in the nuclear location of the PPARG gene were observed when we compared undifferentiated mesenchymal stem cells with mature adipocytes. The gene moved from the nuclear periphery to the nuclear center as its transcriptional activity increased. The RNA/DNA-FISH approach shows that differences in primary transcript production correlated with the allele’s nuclear positioning. Transcriptionally active alleles preferentially occupy the central part of the nucleus, while inactive alleles are found on the nuclear periphery. We also show that transcription of PPARG begins with one allele, but that both alleles are active in later stages of differentiation. Our results provide evidence that functionally distinct alleles of the PPARG gene are positioned in different parts of the cell nucleus. This confirms the importance of nuclear architecture to the regulation of PPARG gene transcription, and thus to the fate of the adipose cell.Electronic supplementary materialThe online version of this article (10.1007/s10577-019-09604-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The importance of the nuclear positioning of the PPARG gene for its expression during porcine in vitro adipogenesis

et al. 2019

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“…This is the first study that shows differential allelic expression of ACACA , LEP , SCD , and TNF in fat deposits and skeletal muscle of postnatal pigs. The recently reported allelic imbalance of two genes, PPARA and PPARGC1A , out of four analyzed (Stachowiak et al 2018 ) suggests that this phenomenon may be widespread among genes involved in regulating lipid metabolism in pigs. Interestingly, SCD was previously shown as imbalanced in porcine prenatal skeletal muscle, whereas LEP but not FASN , SCD , and TNF displayed differential allelic expression in bovine liver, pituitary, and kidney (Olbromski et al 2013 ; Yang et al 2016 ).…”

Section: Resultsmentioning

confidence: 98%

Analysis of allele-specific expression of seven candidate genes involved in lipid metabolism in pig skeletal muscle and fat tissues reveals allelic imbalance of ACACA, LEP, SCD, and TNF

Stachowiak

Flisikowski

2019

J Appl Genetics

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Analysis of allele-specific expression may help to elucidate the genetic architecture of complex traits including fat deposition in pigs. Here, we used pyrosequencing to investigate the allele proportions of candidate genes ( ACACA , ADIPOR1 , FASN , LEP , ME1 , SCD , and TNF ) involved in regulation of lipid metabolism in two fat deposits (subcutaneous and visceral fat) and longissimus dorsi muscle of pigs representing Polish Large White, Polish Landrace, Duroc, and Pietrain breeds. We detected differential allelic expression of ACACA , LEP , SCD , and TNF in all tissues analyzed. To search for putative cis -regulatory elements involved in allele-specific expression, we quantified the methylation level within CpG islands located in 5′-flanking regions of ACACA and SCD . Comparison between samples showing markedly disproportionate allelic expression and control groups with similar levels of both alleles did not reveal significant differences. We also assessed the association of rs321308225 (c.*195C>A) an SNP located in the 3′UTR of ACACA with its allelic expression in Polish Landrace pigs, but it was not significant. We conclude that allelic imbalance occurs frequently in regard to genes involved in regulation of lipid deposition in pigs, and further studies are necessary to identify cis -regulatory elements affecting ACACA , LEP , SCD , and TNF expression in porcine fat tissues and skeletal muscle. Electronic supplementary material The online version of this article (10.1007/s13353-019-00485-z) contains supplementary material, which is available to authorized users.

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“…For example, DLK1 was a critical factor in regulating skeletal muscle development and regeneration through Notch dependent 37 . Previous studies found that PPARA was involved in the regulation of fat deposition in porcine subcutaneous fat and longissimus dorsi muscle 38,39 . Besides, myo brillar structural protein myomesin-3 (MYOM3) was not only associated with muscular dystrophy related proteins and muscle strength, which could be a potential biomarker for monitoring of muscular dystrophy, but was hymethylated in ischemic cardiomyopathy 40,41 .…”

Section: Discussionmentioning

confidence: 96%

Analysis of Long Intergenic Non-Coding RNAs Transcriptomic Profiling in Skeletal Muscle Growth During Porcine Embryonic Development

Zhao

Liu

et al. 2021

Preprint

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Skeletal muscle growth plays a critical role during porcine muscle development stages. Genome-wide transcriptome analysis reveals that thousands of long intergenic non-coding RNAs (lincRNAs) have been identified in various species and implicated as crucial regulator involving in epigenetic regulation. However, comprehensive analysis of lincRNAs in embryonic muscle development stages remain still elusive. Here, we investigated the transcriptome profiles of duroc embryonic muscle tissues from days 33, 65, and 90 of gestation using RNA-seq, there were 228 putative lincRNAs identified. Moreover, these lincRNAs exhibit the characteristics of shorter transcripts length, longer exons, less exon numbers and lower expression level compared with protein-coding transcripts. Differential expression analysis showed that a total of 91 lincRNAs and 2638 mRNAs were differentially expressed. In addition, we also performed quantitative trait locus (QTL) mapping analysis for DE lincRNAs, 113 of 120 DE lincRNAs were localized on 2200 QTLs, we observed many QTLs involved in growth and meat quality traits. Furthermore, we predicted potential target genes of DE lincRNAs in cis or trans regulation. Gene ontology and pathway analysis reveals that potential targets of DE lincRNAs mostly were enriched in the processes and pathways related to tissue development, MAPK signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and insulin signaling pathway, which involved in skeletal muscle physiological functions. Based on cluster analysis, a co-expression network analysis of DE lincRNAs and their potential target genes indicated that DE lincRNAs highly regulated protein-coding genes associated with skeletal muscle development. In this study, many of the DE lincRNAs identified may play essential roles in pig muscle growth and muscle mass. Our study provides crucial information for exploring further the molecular mechanisms of lincRNAs during skeletal muscle development.

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Investigation of allele-specific expression of genes involved in adipogenesis and lipid metabolism suggests complex regulatory mechanisms of PPARGC1A expression in porcine fat tissues

Cited by 10 publications

References 46 publications

The importance of the nuclear positioning of the PPARG gene for its expression during porcine in vitro adipogenesis

The importance of the nuclear positioning of the PPARG gene for its expression during porcine in vitro adipogenesis

Analysis of allele-specific expression of seven candidate genes involved in lipid metabolism in pig skeletal muscle and fat tissues reveals allelic imbalance of ACACA, LEP, SCD, and TNF

Analysis of Long Intergenic Non-Coding RNAs Transcriptomic Profiling in Skeletal Muscle Growth During Porcine Embryonic Development

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