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Gene Review

Mest  -  mesoderm specific transcript

Mus musculus

Synonyms: 121a, AA408879, AI256745, Mesoderm-specific transcript protein, Paternally-expressed gene 1 protein, ...
 
 
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Disease relevance of Mest

 

High impact information on Mest

  • Peg1/Mest imprinted gene on chromosome 6 identified by cDNA subtraction hybridization [3].
  • In a systematic screen using subtraction hybridization between cDNAs from normal and parthenogenetic embryos, we initially identified two apparently novel imprinted genes, Peg1 and Peg3 [3].
  • These epigenetic modifications were heritable and affected gene expression as judged by re-activation of the silent maternal allele of Peg1/Mest imprinted gene in the somatic nucleus [4].
  • Genomic structure and parent-of-origin-specific methylation of Peg1 [5].
  • The genomic structure of Peg1 as well as the DNA sequence of the 5'-end of the gene, including 2.4 kb of promoter sequences and covering the first 2 exons, have been determined [5].
 

Biological context of Mest

  • Effect of CpG methylation on expression of the mouse imprinted gene Mest [2].
  • These results suggest a suppressive role for DNA methylation in Mest expression [2].
  • Furthermore, a methylated reporter construct with the luciferase gene under the control of the putative promoter region of Mest was not competent to produce luciferase activity in MC12 cells [2].
  • Ectopic expression of Mest in 3T3-L1 cells caused increased gene expression of adipose markers such as PPARgamma, CCAAT/enhancer binding protein (C/EBP)alpha, and adipocyte fatty acid binding protein (aP)2 [1].
  • Taken together, the data suggest that there are probably two modes of regulation for the Mest gene; one being a methylation-dependent mechanism that regulates imprinted expression of Mest during development, and the other being a methylation-independent mechanism that is involved in down-regulation of Mest in adult tissues [2].
 

Anatomical context of Mest

  • We identified regions in the maternally imprinted genes (Snrpn, Mest, and Peg3) that were unmethylated in sperm but 100% methylated in mature oocytes [6].
  • In transgenic mice overexpressing Mest in adipose tissue, enhanced expression of the adipose genes was observed [1].
  • Thus Mest appears to enlarge adipocytes and could be a novel marker of the size of adipocytes [1].
  • We previously reported isolation of the mouse gene, Mest (mesoderm-specific transcripts), which is mapped to the proximal part of chromosome 6 and predominantly expressed in the mesoderm and its derivatives during development [2].
  • One such gene, Mest, was predicted by those studies to be a direct target of Fgf8 signalling and to be involved in setting up, rather than implementing, the progenitor cell protomap [7].
 

Other interactions of Mest

  • In somatic tissues, the CpG island of the imprinted Peg1/Mest gene is methylated on the maternal allele [8].
  • FISH has mapped Nap1l5 to G-band 6C1, within the sub-proximal imprinting region but several G-bands distal to the Peg1/Mest cluster [9].
  • We analysed the DNA methylation status of differentially methylated regions of the imprinted genes H19, Mest/Peg1 and Igf2R using fully grown germinal vesicle-stage oocytes (fg oocytes) produced by in vitro folliculogenesis from early preantral follicles [10].
 

Analytical, diagnostic and therapeutic context of Mest

  • Here, we provide evidence that Peg1/Mest is expressed at very low levels in all tissues of adult mice as assessed by RT-PCR [11].
  • Mest and Peg3, two imprinted genes that are paternally expressed, have been disrupted by gene targeting and show high levels of expression in regions where androgenetic cells accumulated, namely the hypothalamus, preoptic area and septum [12].

References

  1. Mest/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size. Takahashi, M., Kamei, Y., Ezaki, O. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  2. Effect of CpG methylation on expression of the mouse imprinted gene Mest. Nishita, Y., Sado, T., Yoshida, I., Takagi, N. Gene (1999) [Pubmed]
  3. Peg1/Mest imprinted gene on chromosome 6 identified by cDNA subtraction hybridization. Kaneko-Ishino, T., Kuroiwa, Y., Miyoshi, N., Kohda, T., Suzuki, R., Yokoyama, M., Viville, S., Barton, S.C., Ishino, F., Surani, M.A. Nat. Genet. (1995) [Pubmed]
  4. Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells. Tada, M., Tada, T., Lefebvre, L., Barton, S.C., Surani, M.A. EMBO J. (1997) [Pubmed]
  5. Genomic structure and parent-of-origin-specific methylation of Peg1. Lefebvre, L., Viville, S., Barton, S.C., Ishino, F., Surani, M.A. Hum. Mol. Genet. (1997) [Pubmed]
  6. Methylation dynamics of imprinted genes in mouse germ cells. Lucifero, D., Mertineit, C., Clarke, H.J., Bestor, T.H., Trasler, J.M. Genomics (2002) [Pubmed]
  7. Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap. Sansom, S.N., Hébert, J.M., Thammongkol, U., Smith, J., Nisbet, G., Surani, M.A., McConnell, S.K., Livesey, F.J. Development (2005) [Pubmed]
  8. Dynamic CpG and non-CpG methylation of the Peg1/Mest gene in the mouse oocyte and preimplantation embryo. Imamura, T., Kerjean, A., Heams, T., Kupiec, J.J., Thenevin, C., Pàldi, A. J. Biol. Chem. (2005) [Pubmed]
  9. A reassessment of imprinting regions and phenotypes on mouse chromosome 6: Nap1l5 locates within the currently defined sub-proximal imprinting region. Beechey, C.V. Cytogenet. Genome Res. (2004) [Pubmed]
  10. In vitro follicular growth affects oocyte imprinting establishment in mice. Kerjean, A., Couvert, P., Heams, T., Chalas, C., Poirier, K., Chelly, J., Jouannet, P., Paldi, A., Poirot, C. Eur. J. Hum. Genet. (2003) [Pubmed]
  11. Analysis of Peg1/Mest imprinting in the mouse. Reule, M., Krause, R., Hemberger, M., Fundele, R. Dev. Genes Evol. (1998) [Pubmed]
  12. Genomic imprinting and the maternal brain. Keverne, E.B. Prog. Brain Res. (2001) [Pubmed]
 
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