Methyltransferase DNMT2 is suggested to be involved in the regulation of numerous processes, however its biological significance and underlying molecular mechanisms remain elusive. In the present study, we have used WI-38 and BJ human fibroblasts as an in vitro model system to investigate the effects of siRNA-based DNMT2 silencing. DNMT2-depleted cells were found to be sensitive to oxidative stress conditions as judged by increased production of reactive oxygen species and susceptible to DNA damage that resulted in the inhibition of cell proliferation. DNMT2 silencing promoted upregulation of proliferation-related and tumor suppressor miRNAs, namely miR-28-3p, miR-34a-3p, miR-30b-5p, miR-29b-3p, miR-200c-3p, miR-28-5p, miR-379-5p, miR-382-5p, miR-194-5p, miR-193b-3p and miR-409-3p. Moreover, DNMT2 silencing induced cellular senescence and DNMT2 levels were elevated in replicatively senescent cells. Taken together, we found that DNMT2 may take part in the regulation of cell proliferation and longevity in human fibroblasts and speculate that the manipulation of DNMT2 levels that limits cell proliferation may be potentially useful anticancer strategy.
The role of European wild horses in horse domestication is poorly understood. While the fossil record for wild horses in Europe prior to horse domestication is scarce, there have been suggestions that wild populations from various European regions might have contributed to the gene pool of domestic horses. To distinguish between regions where domestic populations are mainly descended from local wild stock and those where horses were largely imported, we investigated patterns of genetic diversity in 24 European horse breeds typed at 12 microsatellite loci. The distribution of high levels of genetic diversity in Europe coincides with the distribution of predominantly open landscapes prior to domestication, as suggested by simulation-based vegetation reconstructions, with breeds from Iberia and the Caspian Sea region having significantly higher genetic diversity than breeds from central Europe and the UK, which were largely forested at the time the first domestic horses appear there. Our results suggest that not only the Eastern steppes, but also the Iberian Peninsula provided refugia for wild horses in the Holocene, and that the genetic contribution of these wild populations to local domestic stock may have been considerable. In contrast, the consistently low levels of diversity in central Europe and the UK suggest that domestic horses in these regions largely derive from horses that were imported from the Eastern refugium, the Iberian refugium, or both.
In the presented research, BovineSNP50 microarrays (Illumina) were applied to determine runs of homozygosity in the genomes of 11 cattle breeds maintained in Poland. These cattle breeds represent three basic utility types: milk, meat and dual purpose. Analysis of runs of homozygosity allowed the evaluation of the level of autozygosity within each breed in order to calculate the genomic inbreeding coefficient (FROH), as well as to identify regions of the genome with a high frequency of ROH occurrence, which may reflect traces of directional selectin left in their genomes. Visible differences in the length and distribution of runs of homozygosity in the genomes of the analyzed cattle breeds have been observed. The highest mean number and mean sums of lengths of runs of homozygosity were characteristic for Hereford cattle and intermediate for the Holstein-Friesian Black-and-White variety, Holstein-Friesian Red-and-White variety, Simmental, Limousin, Montbeliarde and Charolais breeds. However, lower values were observed for cattle of conserved breeds. Moreover, the selected livestock differed in the level of inbreeding estimated using the FROH coefficient. In regions of the genome with a high frequency of ROH occurrence, which may reflect the impact of directional selection, a number of genes were observed that can be potentially related to the production traits which are under selection pressure for specific production types. The most important detected genes were GHR, MSTN, DGAT1, FABP4, and TRH, with a known influence on the milk and meat traits of the studied cattle breeds.
Cytogenetic and molecular genetic studies of an intersex horse have been carried out. The investigated animal had overall male body conformation; however, its external genitalia consisted of incompletely developed vulva and penis. The X and Y chromosome painting probes detected three cell lines in the examined horse: 63,X, 64,XX and 65,XX with a fragment of a Y chromosome (del Y). The DNA analysis with the PCR and PCR/RFLP methods showed absence of SRY,AMELY and ZFY genes as well as of six Y microsatellite markers (YM2, YP9, YJ10, YE1, YH12, and YA16). These results suggest that the Y chromosome fragment detected in the investigated animal was the result of a deletion of a euchromatic fragment comprising the above-mentioned markers.