Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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PGC methylome analysis revealed large, germline-specific mouse hypomethylated DNA domains with unique genomic and epigenomic features

ABSTRACT: With the goal of understanding the epigenetic regulation required for germ cell-specific gene expression, we devised a method of DNA methylation analysis adapted for a small number of developing germ cells. This microarray-based method provides the genome-wide assay of DNA methylation using a sub-nanogram quantity of genomic DNA. Using this technique, we obtained DNA methylation profiles for mouse germ cells in various developmental stages including primordial germ cells (PGC) and for stem cells derived from embryos or germ cells. Cluster analysis of the data revealed that each cell type possesses its own characteristic DNA methylation profile, enabling classification of the cell types. This classification is generally consistent with that based on gene expression profiles except for primordial germ cells, whose genome is globally hypomethylated. Among the differentially methylated sites thus identified, we focused on a group of genomic sequences hypomethylated specifically in germline cells. These hypomethylated sequences tend to be clustered, forming large (10 kb to ~9 Mb) genomic domains. Most of these hypomethylated regions designated here as Large Hypomethylated Domain (LoD) correspond to segmentally duplicated regions that contain gene families showing germ cell-specific expression. These include mouse orthologues of human cancer testis antigen genes. Most LoDs appear to be enriched with H3 lysine 9 dimethylation (H3K9me2), usually regarded as a repressive histone modification. It thus appears t hat such a unique epigenomic state (i.e., DNA hypomethylation with H3K9me2 enrichment) may be a prerequisite for the expression of genes contained in these genomic domains. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Rieko Ikeda

PROVIDER: E-GEOD-39895 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:MarekM-bM-^@M-^Ys disease virus (MDV) is an oncovirus causing tumor disease known as MarekM-bM-^@M-^Ys disease (MD) in chicken. Breeding of chickens genetically resistant to MD is considered a vital augment to better control MD. To find the mechanism underlying the genetic resistance to MD, a genomic structural variation, copy number variation (CNV), was examined in inbred MD-resistant and -susceptible chicken lines by using the comparative genomic hybridization (CGH) technique. A total of 45 copy number variation regions (CNVRs) were found spanning across 3,297,038 bp in length of the chicken genome in 4 lines of chickens. Ten CNVRs were selectively confirmed with quantitative real-time PCR. The comparison between the resistant and susceptible chicken lines revealed 28 differentially presented CNVRs, which are functionally involved in immune response, cell proliferation in midbrain, G-protein coupled receptor signaling pathway, and protein-glutamine gamma-glutamyltransferase activity. Two CNVRs that are related with MD-resistance and M-bM-^@M-^Ssusceptibility were also found transmitted to descendent recombinant congenic lines that differ in susceptibility to MD. A positive correlation was identified between the CNVRs and gene expression, indicating the importance of gene expression dosage in disease resistance. We also found the overlapping between the CNVR region and the MarekM-bM-^@M-^Ys disease trait related quantitative trait loci (QTLs). In conclusion, our data provided additional information elucidating one of possible mechanisms underlying of genetic resistance to MD. The findings may eventually lead to better strategies for genetic improvement of resistance to MD in poultry. L63: highly resistant to MD; L72: highly susceptible to MD; RCS-L: moderate resistant to MD; RCS-M: moderate susceptible to MD Red blood cell DNAs were isolated from L63, L72, RCS-L and RCS-M and then labeled with Cy3. DNA from Red Junglefowl was labeled with Cy5 as reference and mixed with Cy3 labeled DNA, then hybridized to the 385K chicken tiling array. The hybridization, normalization and segmentation analysis were performed by NimbleGen Systems Inc. (Madison, USA). A detailed description of their technical specifics can be found on http://www.nimblegen.com/products/lit/lit.html. Briefly, the segments with five or more probes having a mean log2 ratio greater than M-BM-10.5 (0.5_5) were chosen as candidate CNVs.

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PGC methylome analysis revealed large, germline-specific mouse hypomethylated DNA domains with unique genomic and epigenomic features

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