Skip to main content

Advertisement

Log in

MyoD promotes porcine PPARγ gene expression through an E-box and a MyoD-binding site in the PPARγ promoter region

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a key transcription factor in adipogenesis and can be regulated by adipogenesis-related factors. However, little information is available regarding its regulation by myogenic factors. In this study, we found that over-expression of MyoD enhanced porcine adipocyte differentiation and up-regulated PPARγ expression, whereas small interfering RNA against MyoD significantly attenuated porcine adipocyte differentiation and inhibited PPARγ expression. The MyoD-binding sites in the PPARγ promoter region at −412 to −396 and −155 to −150 were identified by promoter deletion analysis and site-directed mutagenesis. Electrophoretic mobility shift assays and chromatin immunoprecipitation further showed that these two regions are MyoD-binding sites, both in vitro and in vivo, indicating that MyoD directly interacts with the porcine PPARγ promoter. Thus, our results demonstrate that an Enhancer box and a binding site for a cooperative co-activator of MyoD are present in the promoter region of porcine PPARγ; furthermore, MyoD up-regulates PPARγ expression and promotes porcine adipocyte differentiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Albu JB, Kovera AJ, Allen L, Wainwright M, Berk E, Raja-Khan N, Janumala I, Burkey B, Heshka S, Gallagher D (2005) Independent association of insulin resistance with larger amounts of intermuscular adipose tissue and a greater acute insulin response to glucose in African American than in white nondiabetic women. Am J Clin Nutr 82:1210–1217

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bergstrom DA, Penn BH, Strand A, Perry RL, Rudnicki MA, Tapscott SJ (2002) Promoter-specific regulation of MyoD binding and signal transduction cooperate to pattern gene expression. Mol Cell 9:587–600

    Article  CAS  PubMed  Google Scholar 

  • Buckingham M, Rigby PW (2014) Gene regulatory networks and transcriptional mechanisms that control myogenesis. Dev Cell 28:225–238. doi:10.1016/j.devcel.2013.12.020

    Article  CAS  PubMed  Google Scholar 

  • Busanello A, Battistelli C, Carbone M, Mostocotto C, Maione R (2012) MyoD regulates p57kip2 expression by interacting with a distant cis-element and modifying a higher order chromatin structure. Nucleic Acids Res 40:8266–8275. doi:10.1093/nar/gks619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chmielewska-Kassassir M, Wozniak LA, Ogrodniczek P, Wojcik M (2013) The role of peroxisome proliferator-activated receptors gamma (PPARgamma) in obesity and insulin resistance. Postepy Hig Med Dosw 67:1283–1299

    Article  Google Scholar 

  • Choi J, Costa ML, Mermelstein CS, Chagas C, Holtzer S, Holtzer H (1990) MyoD converts primary dermal fibroblasts, chondroblasts, smooth muscle, and retinal pigmented epithelial cells into striated mononucleated myoblasts and multinucleated myotubes. Proc Natl Acad Sci U S A 87:7988–7992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng B, Wen JH, Ding Y, Peng J, Jiang SW (2012a) Different regulation role of myostatin in differentiating pig ADSCs and MSCs into adipocytes. Cell Biochem Funct 30:145–150. doi:10.1002/cbf.1828

    Article  CAS  PubMed  Google Scholar 

  • Deng B, Wen J, Ding Y, Gao Q, Huang H, Ran Z, Qian Y, Peng J, Jiang S (2012b) Functional analysis of pig myostatin gene promoter with some adipogenesis- and myogenesis-related factors. Mol Cell Biochem 363:291–299. doi:10.1007/s11010-011-1181-y

    Article  CAS  PubMed  Google Scholar 

  • Fajas L, Fruchart JC, Auwerx J (1998) PPARgamma3 mRNA: a distinct PPARgamma mRNA subtype transcribed from an independent promoter. FEBS Lett 438:55–60

    Article  CAS  PubMed  Google Scholar 

  • Fong AP, Tapscott SJ (2013) Skeletal muscle programming and re-programming. Curr Opin Genet Dev 23:568–573. doi:10.1016/j.gde.2013.05.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fong AP, Yao Z, Zhong JW, Cao Y, Ruzzo WL, Gentleman RC, Tapscott SJ (2012) Genetic and epigenetic determinants of neurogenesis and myogenesis. Dev Cell 22:721–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fong AP, Yao Z, Zhong JW, Johnson NM, Farr GH 3rd, Maves L, Tapscott SJ (2015) Conversion of MyoD to a neurogenic factor: binding site specificity determines lineage. Cell Rep 10:1937–1946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fox KE, Fankell DM, Erickson PF, Majka SM, Crossno JT Jr, Klemm DJ (2006) Depletion of cAMP-response element-binding protein/ATF1 inhibits adipogenic conversion of 3T3-L1 cells ectopically expressing CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, or PPAR gamma 2. J Biol Chem 281:40341–40353. doi:10.1074/jbc.M605077200

    Article  CAS  PubMed  Google Scholar 

  • Goodpaster BH, Krishnaswami S, Resnick H, Kelley DE, Haggerty C, Harris TB, Schwartz AV, Kritchevsky S, Newman AB (2003) Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 26:372–379

    Article  PubMed  Google Scholar 

  • Goudenege S, Pisani DF, Wdziekonski B, Di Santo JP, Bagnis C, Dani C, Dechesne CA (2009) Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD. Mol Ther 17:1064–1072. doi:10.1038/mt.2009.67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grindflek E, Sundvold H, Klungland H, Lien S (1998) Characterisation of porcine peroxisome proliferator-activated receptors gamma 1 and gamma 2: detection of breed and age differences in gene expression. Biochem Biophys Res Commun 249:713–718. doi:10.1006/bbrc.1998.9212

    Article  CAS  PubMed  Google Scholar 

  • Harper GS, Pethick DW (2004) How might marbling begin? Aust J Exp Agric 44:653–662

    Article  Google Scholar 

  • Huangfu Y, Zan L, Wang H, Cheng G, Liu Y, Gao J, Li Y, Yang N (2014) Insulin induced adipogenic differentiation of bovine myoblasts. J Northwest A&F Univ (Nat Sci Ed) 42:1

    Google Scholar 

  • Hudson NJ, Reverter A, Greenwood PL, Guo B, Cafe LM, Dalrymple BP (2015) Longitudinal muscle gene expression patterns associated with differential intramuscular fat in cattle. Animal 9:650–659. doi:10.1017/s1751731114002754

    Article  CAS  PubMed  Google Scholar 

  • Ikeda K, Takayama T, Suzuki N, Shimada K, Otsuka K, Ito K (2006) Effects of low-intensity pulsed ultrasound on the differentiation of C2C12 cells. Life Sci 79:1936–1943

    Article  CAS  PubMed  Google Scholar 

  • Kazama T, Fujie M, Endo T, Kano K (2008) Mature adipocyte-derived dedifferentiated fat cells can transdifferentiate into skeletal myocytes in vitro. Biochem Biophys Res Commun 377:780–785. doi:10.1016/j.bbrc.2008.10.046

    Article  CAS  PubMed  Google Scholar 

  • Kim HS, Liang L, Dean RG, Hausman DB, Hartzell DL, Baile CA (2001) Inhibition of preadipocyte differentiation by myostatin treatment in 3T3-L1 cultures. Biochem Biophys Res Commun 281:902–906. doi:10.1006/bbrc.2001.4435

    Article  CAS  PubMed  Google Scholar 

  • Kim SW, Her SJ, Kim SY, Shin CS (2005) Ectopic overexpression of adipogenic transcription factors induces transdifferentiation of MC3T3-E1 osteoblasts. Biochem Biophys Res Commun 327:811–819. doi:10.1016/j.bbrc.2004.12.076

    Article  CAS  PubMed  Google Scholar 

  • Kitzmann M, Fernandez A (2001) Crosstalk between cell cycle regulators and the myogenic factor MyoD in skeletal myoblasts. Cell Mol Life Sci 58:571–579

    Article  CAS  PubMed  Google Scholar 

  • Lai PH, Wang WL, Ko CY, Lee YC, Yang WM, Shen TW, Chang WC, Wang JM (2008) HDAC1/HDAC3 modulates PPARG2 transcription through the sumoylated CEBPD in hepatic lipogenesis. Biochim Biophys Acta 1783:1803–1814. doi:10.1016/j.bbamcr.2008.06.008

    Article  CAS  PubMed  Google Scholar 

  • Lee YH, Kim SH, Lee YJ, Kang ES, Lee BW, Cha BS, Kim JW, Song DH, Lee HC (2013) Transcription factor snail is a novel regulator of adipocyte differentiation via inhibiting the expression of peroxisome proliferator-activated receptor gamma. Cell Mol Life Sci 70:3959–3971. doi:10.1007/s00018-013-1363-8

    Article  CAS  PubMed  Google Scholar 

  • Lefterova MI, Haakonsson AK, Lazar MA, Mandrup S (2014) PPARgamma and the global map of adipogenesis and beyond. Trends Endocrinol Metab 25:293–302. doi:10.1016/j.tem.2014.04.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu M, Peng J, Xu DQ, Zheng R, Li FE, Li JL, Zuo B, Lei MG, Xiong YZ, Deng CY, Jiang SW (2008) Association of MYF5 and MYOD1 gene polymorphisms and meat quality traits in large white × Meishan F2 pig populations. Biochem Genet 46:720–732. doi:10.1007/s10528-008-9187-1

    Article  CAS  PubMed  Google Scholar 

  • Maione R, Amati P (1997) Interdependence between muscle differentiation and cell-cycle control. Biochim Biophys Acta 1332:M19–M30

    CAS  PubMed  Google Scholar 

  • Naka A, Iida KT, Nakagawa Y, Iwasaki H, Takeuchi Y, Satoh A, Matsuzaka T, Ishii KA, Kobayashi K, Yatoh S, Shimada M, Yahagi N, Suzuki H, Sone H, Yamada N, Shimano H (2013) TFE3 inhibits myoblast differentiation in C2C12 cells via down-regulating gene expression of myogenin. Biochem Biophys Res Commun 430:664–669. doi:10.1016/j.bbrc.2012.11.094

    Article  CAS  PubMed  Google Scholar 

  • Omi T, Brenig B, Spilar Kramer S, Iwamoto S, Stranzinger G, Neuenschwander S (2005) Identification and characterization of novel peroxisome proliferator-activated receptor-gamma (PPAR-gamma) transcriptional variants in pig and human. J Anim Breed Genet 122:45–53

    Article  CAS  PubMed  Google Scholar 

  • Pethick DW, Harper GS, Oddy VH (2004) Growth, development and nutritional manipulation of marbling in cattle: a review. Aust J Exp Agric 44:705–715. doi:10.1071/ea02165

    Article  Google Scholar 

  • Rosen ED (2005) The transcriptional basis of adipocyte development. Prostaglandins Leukot Essent Fatty Acids 73:31–34. doi:10.1016/j.plefa.2005.04.004

    Article  CAS  PubMed  Google Scholar 

  • Serria MS, Ikeda H, Omoteyama K, Hirokawa J, Nishi S, Sakai M (2003) Regulation and differential expression of the c-maf gene in differentiating cultured cells. Biochem Biophys Res Commun 310:318–326

    Article  CAS  PubMed  Google Scholar 

  • Singh K, Cassano M, Planet E, Sebastian S, Jang SM, Sohi G, Faralli H, Choi J, Youn HD, Dilworth FJ, Trono D (2015) A KAP1 phosphorylation switch controls MyoD function during skeletal muscle differentiation. Genes Dev 29:513–525. doi:10.1101/gad.254532.114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tontonoz P, Spiegelman BM (2008) Fat and beyond: the diverse biology of PPAR gamma. Annu Rev Biochem 77:289–312

    Article  CAS  PubMed  Google Scholar 

  • Tontonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79:1147–1156

    Article  CAS  PubMed  Google Scholar 

  • Weintraub H, Tapscott SJ, Davis RL, Thayer MJ, Adam MA, Lassar AB, Miller AD (1989) Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci U S A 86:5434–5438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weintraub H, Davis R, Lockshon D, Lassar A (1990) MyoD binds cooperatively to two sites in a target enhancer sequence: occupancy of two sites is required for activation. Proc Natl Acad Sci U S A 87:5623–5627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yagi M, Suzuki N, Takayama T, Arisue M, Kodama T, Yoda Y, Otsuka K, Ito K (2009) Effects of lactoferrin on the differentiation of pluripotent mesenchymal cells. Cell Biol Int 33:283–289

    Article  CAS  PubMed  Google Scholar 

  • Yamanouchi K, Ban A, Shibata S, Hosoyama T, Murakami Y, Nishihara M (2007) Both PPAR gamma and C/EBP alpha are sufficient to induce transdifferentiation of goat fetal myoblasts into adipocytes. J Reprod Dev 53:563–572. doi:10.1262/jrd.18169

    Article  CAS  PubMed  Google Scholar 

  • Yan C, Xia X, He J, Ren Z, Xu D, Xiong Y, Zuo B (2015) MyoD is a novel activator of porcine FIT1 gene by interacting with the canonical E-Box element during myogenesis. Int J Mol Sci 16:25014–25030

    Article  PubMed  PubMed Central  Google Scholar 

  • Yanagisawa M, Suzuki N, Mitsui N, Koyama Y, Otsuka K, Shimizu N (2007) Effects of compressive force on the differentiation of pluripotent mesenchymal cells. Life Sci 81:405–412

    Article  CAS  PubMed  Google Scholar 

  • Yu YH, Liu BH, Mersmann HJ, Ding ST (2006) Porcine peroxisome proliferator-activated receptor gamma induces transdifferentiation of myocytes into adipocytes. J Anim Sci 84:2655–2665. doi:10.2527/jas.2005-645

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Deng B, Wen J, Chen K, Liu W, Ye S, Huang H, Jiang S, Xiong Y (2015) PPARgamma and MyoD are differentially regulated by myostatin in adipose-derived stem cells and muscle satellite cells. Biochem Biophys Res Commun 458:375–380. doi:10.1016/j.bbrc.2015.01.120

    Article  CAS  PubMed  Google Scholar 

  • Zhao X, Mo D, Li A, Gong W, Xiao S, Zhang Y, Qin L, Niu Y, Guo Y, Liu X, Cong P, He Z, Wang C, Li J, Chen Y (2011) Comparative analyses by sequencing of transcriptomes during skeletal muscle development between pig breeds differing in muscle growth rate and fatness. PLoS One 6:e19774. doi:10.1371/journal.pone.0019774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Siwen Jiang.

Additional information

Bing Deng and Feng Zhang contributed equally to this work.

This research was supported by the National Natural Science Foundation of China (31201766, 31472075 and 31272425), the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAD20B01 and 2011BAD28B01) and the Science and Technology Planning Project of Hubei Province, China (2014ABA025).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deng, B., Zhang, F., Chen, K. et al. MyoD promotes porcine PPARγ gene expression through an E-box and a MyoD-binding site in the PPARγ promoter region. Cell Tissue Res 365, 381–391 (2016). https://doi.org/10.1007/s00441-016-2380-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-016-2380-3

Keywords

Navigation