Project description:This SuperSeries is composed of the following subset Series: GSE26720: Chromosome wide analysis of parental allele specific chromatin and DNA methylation GSE26891: Chromosome wide analysis of parental allele specific chromatin and DNA methylation along mouse distal chr7 GSE26892: Chromosome wide analysis of parental allele specific chromatin and DNA methylation along the central part of mouse chr7 GSE26893: Chromosome wide analysis of parental allele specific chromatin and DNA methylation along mouse distal chr15 Refer to individual Series
Project description:Despite extensive progress in Huntingtonâ??s Disease (HD) research, very little is known about the association of epigenetic variation and HD pathogenesis in human brain tissues. Moreover, its contribution to the tissue-specific transcriptional regulation of the huntingtin gene (HTT), in which HTT expression levels are highest in brain and testes, is currently unknown. To investigate the role of DNA methylation in HD pathogenesis and tissue-specific expression of HTT, we utilized the Illumina HumanMethylation450K BeadChip array to measure DNA methylation in a cohort of age-matched HD and control human cortex and liver tissues. In cortex samples, we found minimal evidence of HD-associated DNA methylation at probed sites after correction for cell heterogeneity but did observe an association to age of disease onset. By contrast, comparison of matched cortex and liver samples revealed tissue-specific DNA methylation of the HTT gene region at 38 sites (FDR < 0.05). Importantly, we identified a novel differentially methylated binding site in the HTT proximal promoter for the transcription factor CTCF. This CTCF site displayed increased occupancy in cortex, where HTT expression is higher, compared to liver. Additionally, CTCF silencing reduced the activity of a HTT promoter-reporter construct, suggesting that CTCF plays a role in regulating HTT promoter function. Overall, although we were unable to detect HD-associated DNA methylation alterations at queried sites, we found that DNA methylation may be correlated to age of disease onset in cortex tissues. Moreover, our data suggest that DNA methylation may, in part, contribute to tissue-specific HTT transcription through differential CTCF occupancy. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain genome-wide DNA methylation measures in human cortex tissue (n = 13), with a subset of matched liver tissues (n = 5) , from a cohort of HD (n = 7) and control (n = 6) individuals in order to identify potential HD-related DNA methylation aberration in the brain as well as tissue-specific DNA methylation variation at the HTT gene locus.
Project description:Study hypothesis: Increasing folate status and the MethyleneTetraHydroFolate Reductase (MTHFR) C677T genotype influence intermediary biomarkers of preclinical neoplasia (DeoxyriboNucleic Acid [DNA] methylation and uracil misincorporation) in human colonic epithelium.
Primary outcome(s): Changes in genomic and gene specific DNA methylation and uracil misincorporation.
Project description:DNA methylation is the major repression mechanism for human retrotransposons, such as the Alu family. Here, we have derived methylation levels regarding 5238 loci belonging to two Alu subfamilies, AluYa5 and AluYb8, using High-Throughput Targeted Repeat Element Bisulfite Sequencing (HT-TREBS). The results indicate that ~90% of loci are repressed by high methylation levels. Of the remaining loci, many of these hypomethylated elements are found near gene promoters and show high levels of DNA methylation variation. We have characterized this variation in the context of tumorigenesis and inter-individual differences. Comparison of a primary breast tumor and its matched normal tissue revealed early DNA methylation changes in ~1% of AluYb8 elements in response to tumorigenesis. At the same time, AluYa5/Yb8 elements proximal to promoters also showed differences in methylation of up to one order of magnitude even between normal individuals. Overall, the current study demonstrates that early loss of methylation occurs during tumorigenesis in a subset of young Alu elements, suggesting their potential clinical relevance. However, techniques such as deep-bisulfite-sequencing of individual loci using HT-TREBS are required to distinguish clinically relevant loci from the background observed for AluYa5/Yb8 elements in general with regard to high levels of inter-individual variation in DNA methylation. HT-TREBS has been used with the Ion Torrent PGM platform to analyze the DNA methylation of 5238 AluYa5/Yb8 elements in a locus-specific manner in human skin-derived fibroblast cells, and a matched normal breast and primary tumor
Project description:DNA methylation is very important for mammalian development. However, it is unclear whether the DNA methylation pattern is evolutionarily conserved. The Y-chromosome serves as a powerful tool for the study of human evolution because it is only transferred between males. In this study, based on deep-rooted pedigrees and the latest Y-chromosome phylogenetic tree, we performed epigenetic pattern analysis of Y-chromosome from 72 donors. By comparing their respective DNA methylation levels, we found that the DNA methylation pattern on the Y-chromosome was stable among family members and within haplogroups. Despite two haplogroup-specific methylation sites were found, they were both genotype-dependent. Moreover, with a remote divergence time, the African and Asian samples also had similar DNA methylation patterns. Our findings indicated that the DNA methylation pattern on Y-chromosome was conservative during human male history.
Project description:Imprinted genes are monoallelically expressed according to parental inheritance. The maternally and paternally inherited alleles are distinguished epigenetically by DNA methylation and histone modifications. Chromosome-wide Chromatin immunoprecipitation (ChIP) and MIRA analysis of MatDup.dist7 and PatDup.dist7 MEFs provided a panoramic map of reciprocal allele-specific histone modifications and DNA methylation at imprinted genes along distal chromosome 7 and 15. ChIP-chip and MIRA-chip was done to map histone modifications and DNA methylation along central chr7 in the maternal allele and paternal allele in Matdup.dist7 and Patdup.dist7 MEFs, respectively, using Nimblegen tiling arrays for central chr7.
Project description:Imprinted genes are monoallelically expressed according to parental inheritance. The maternally and paternally inherited alleles are distinguished epigenetically by DNA methylation and histone modifications. Chromosome-wide Chromatin immunoprecipitation (ChIP) and MIRA analysis of MatDup.dist7 and PatDup.dist7 MEFs provided a panoramic map of reciprocal allele-specific histone modifications and DNA methylation at imprinted genes along distal chromosome 7 and 15. ChIP-chip and MIRA-chip was done to map histone modifications and DNA methylation along distal chr15 in the maternal allele and paternal allele in Patdup.dist7=MatDup.dist15 and Patdup.dist7=MatDupdis15 MEFs, respectively, using Nimblegen tiling arrays for chr15.