Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Chromatin and Sequence Features that Define the Fine and Gross Structure of Genomics Methylation Patterns

ABSTRACT: We report a new method for genome-wide methylation profiling that is able to probe methylation status in both single-copy DNA and interspersed repeats. This method, MethylMAPS, uses methylation-sensitive and -dependent enzymes to fractionate the genome according to methylation state. Methylated and unmethylated fragments are then sequenced with Next-Gen sequencing to map methylated and unmethylated CpG sites in the genome. We have used this method to determine the methylation status of >275 million CpG sites in human and mouse DNA from breast and brain tissues. We conclude that methylation is the default state of most CpG dinucleotides and that a combination of local dinucleotide frequencies, the interaction of repeated sequences, and the presence or absence of histone variants or modifications shields a population of CpG sites (most of which are in and around promoters) from DNA methyltransferases that lack intrinsic sequence specificity. Genome-wide methylation mapping in two normal human breast tissues, human brain tissue and mouse brain tissue.

ORGANISM(S): Mus musculus

SUBMITTER: John Edwards

PROVIDER: E-GEOD-21242 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Chromatin and sequence features that define the fine and gross structure of genomic methylation patterns.

Edwards John R JR O'Donnell Anne H AH Rollins Robert A RA Peckham Heather E HE Lee Clarence C Milekic Maria H MH Chanrion Benjamin B Fu Yutao Y Su Tao T Hibshoosh Hanina H Gingrich Jay A JA Haghighi Fatemeh F Nutter Robert R Bestor Timothy H TH

Genome research 20100520 7

Abnormalities of genomic methylation patterns are lethal or cause disease, but the cues that normally designate CpG dinucleotides for methylation are poorly understood. We have developed a new method of methylation profiling that has single-CpG resolution and can address the methylation status of repeated sequences. We have used this method to determine the methylation status of >275 million CpG sites in human and mouse DNA from breast and brain tissues. Methylation density at most sequences was ...[more]

PMID: 20488932

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Project description:We assessed DNA methylation and copy number status of 27,000 CpGs in 149 urothelial carcinomas and integrated the findings with gene expression and mutation data. Methylation was associated with gene expression for 1,332 CpGs, of which 26% showed positive correlation with expression, i.e., high methylation and high gene expression levels. These positively correlated CpGs were part of specific transcription factor binding sites, such as sites for MYC and CREBP1, or located in gene bodies. Furthermore, we found genes with copy number gains, low expression and high methylation levels, revealing an association between methylation and copy number levels. This phenomenon was typically observed for developmental genes, such as HOX genes and tumor suppressor genes. In contrast, we also identified genes with copy number gains, high expression and low methylation levels. This was for instance observed for some keratin genes. Tumor cases could be grouped into four subgroups, termed epitypes, by their DNA methylation profiles. One epitype was influenced by the presence of infiltrating immune cells, two epitypes were mainly composed of non-muscle invasive tumors, and the remaining epitype of muscle invasive tumors. The polycomb complex protein EZH2 that blocks differentiation in embryonic stem cells showed increased expression both at the mRNA and protein levels in the muscle invasive epitype, together with methylation of polycomb target genes and HOX genes. Our data highlights HOX gene silencing and EZH2 expression as mechanisms to promote a more undifferentiated and aggressive state in UC. The study was conducted on genomic DNA from 150 primary fresh-frozen urothelial carcinoma tumors selected to have equal representation of stages Ta, T1 and T2>. The design also included four fully methylated and four unmethylated hybridization controls as well as 7 Normal urothelium samples. One tumor sample (UC_0556_1) was included as a technical replicate in each of four bisulfite treatment batches. The samples were bisulfite treated and hybridized to Illumina Human Methylation27 Bead Chip arrays according to manufacturers instructions at the SCIBLU Genomics Centre at Lund University, Sweden. Note: Illumina methylation data set comprises total of 168 samples (raw data), but 156 samples (processed data), derived from primary urothelial carcinoma samples. See README.txt for details of the 12 samples not included in the final, processed data.

Dataset Information

Chromatin and Sequence Features that Define the Fine and Gross Structure of Genomics Methylation Patterns

Publications

Chromatin and sequence features that define the fine and gross structure of genomic methylation patterns.

Similar Datasets

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