Disease relevance of MEST

• Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma [1].
• Altered expression of PHLDA2 and MEST was not accompanied by changes in DNA methylation within their imprinting centers, and immunohistochemistry showed PHLDA2 protein appropriately restricted to villous and intermediate cytotrophoblast in the IUGR placentae [2].
• Putative loss of imprinting (LOI) of PEG1/MEST has subsequently also been implicated in the aetiology of lung adenocarcinomas and colon cancer [3].
• Frequent loss of imprinting of PEG1/MEST in invasive breast cancer [4].
• In a human choriocarcinoma/trophoblastic tumour grown in a nude mouse, human MEST was expressed in the tumour cells, whereas murine Mest was expressed in endothelia of the murine capillaries [5].

Psychiatry related information on MEST

• In the mouse, Peg1/Mest is associated with embryonic growth and maternal behavior [6].

High impact information on MEST

• To date, three imprinted genes-PEG1/MEST, gamma2-COP, and GRB10-have been identified on chromosome 7, but their role in the etiology of SRS remains uncertain [7].
• The matUPD7 segment at 7q31-qter extends for 35 Mb and includes the imprinted gene cluster of PEG1/MEST and gamma2-COP at 7q32 [7].
• Our results suggest that MESTIT1 is a paternally expressed non-coding RNA that may be involved in the regulation of MEST expression during development [8].
• MEST isoform 1 was determined to be exclusively expressed from the paternal allele in all fetal tissues and cell lines examined, whereas MEST isoform 2 was only preferentially expressed from the paternal allele in a tissue/cell-type-specific manner [8].
• Transcripts located between D7S530 and D7S649 (a 1.5 Mb interval encompassing MEST ) were subjected to RT-PCR analysis using somatic cell hybrids [8].

Chemical compound and disease context of MEST

• These findings indicated that independent deregulation took place in imprinted genes and suggested that aberrant imprinting of IGF2 and MEST was involved in the development of lung adenocarcinoma [1].

Biological context of MEST

• Identification and characterization of an imprinted antisense RNA (MESTIT1) in the human MEST locus on chromosome 7q32 [8].
• PEG1 (or MEST) is an imprinted gene located on human chromosome 7q32 that is expressed predominantly from the paternal allele [6].
• The MEST/PEG1 gene remains unmethylated at all subsequent post-pubertal stages of spermatogenesis, including mature spermatozoa [9].
• The gene TSGA14, adjacent to the imprinted gene MEST, escapes genomic imprinting [10].
• We identified additional MEST 3'-UTR sequence, which overlaps the last four exons and introns of gamma2-COP [11].

Anatomical context of MEST

• LOI of IGF2 and PEG1/MEST was also observed in colorectal mucosa from almost all the patients with LOI in tumor tissue [12].
• Biallelic expression in blood is supported by the demonstration of PEG1/MEST transcripts in a lymphoblastoid cell line with maternal uniparental disomy 7 [13].
• We also searched for imprinting mutations potentially implicated in autism: analysis of both DNA methylation and replication timing indicated a normal imprinting regulation of the PEG1/COPG2 domain in blood lymphocytes of all patients tested [14].
• The PEG1 gene (a.k.a. MEST) is expressed in human placental trophoblast and endothelium, and data from knockout mice show that this gene regulates placental and fetal growth [15].
• Furthermore, we found the demethylation of PEG1 in growing oocytes from some ART-treated infertile women and a gain in the methylation of H19 [16].

Associations of MEST with chemical compounds

• LOI of the insulin-like growth factor 2 gene (IGF2) and mesoderm-specific transcript (MEST, also known as paternally expressed gene 1) was noted in 47% (seven of 15) and 85% (11 of 13) of informative cases, respectively [1].
• Bisulfite conversion/sequencing indicates that the inter-individual differences reflect the relative representation of heavily methylated vs. unmethylated alleles, and RT-PCR/RFLP analysis shows strongly biased allelic expression of PEG1 isoform 2 mRNA in a majority of placentae with a high proportion of methylated alleles [15].

Regulatory relationships of MEST

• PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS [17].

Other interactions of MEST

• One hundred kilobases proximal to MEST lies a group of four carboxypeptidase A (CPA) genes [18].
• The fact that COPG2 and TSGA14, both neighbors of MEST, escape genomic imprinting suggests that the 7q32 imprinted region may be small and not similar to other imprinted domains, such as those at 15q11-13 and 11p15.5 [10].
• Since the COPG2IT1 gene in the vicinity of MEST has been reported to be imprinted, we presumed that TSGA14 might also be imprinted [10].
• Two representative imprinted genes, H19 and MEST/PEG1, were studied [9].
• Three of six genes analysed (SNRPN, PEG1 and UBE3A) are clearly expressed in preimplantation embryos [19].

Analytical, diagnostic and therapeutic context of MEST

• Direct sequence analysis failed to detect any mutations in the PEG1/MEST alpha coding region, and there were no significant mutations in the 5'-flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region [17].
• Based on the differential methylation of the promoter region of the imprinted PEG1/MEST locus at 7q32, we designed a multiplex methylation PCR (mPCR) assay to rapidly distinguish UPD7 from biparental inheritance of chromosome 7 [20].
• PAG1/MEST is an imprinted gene mapping to human chromosome 7q32 [21].

References