Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression analysis of breast cancer (HCC1954) and normal breast cells (HMEC)

ABSTRACT: While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation of tumor suppressors as well as changes in chromatin modifications as caused by genetic mutations of the chromatin-modifying machinery. However, the extent of epigenetic alterations in cancer cells has not been fully characterized. Here, we describe the first complete methylome maps at single nucleotide resolution of a low-passage breast cancer cell line and primary human mammary epithelial cells. We find widespread DNA hypomethylation in the cancer cell, primarily at partially methylated domains (PMDs) in normal breast cells. Unexpectedly, genes within these regions are largely silenced in cancer cells. The loss of DNA methylation in these regions is accompanied by formation of repressive chromatin, with a significant fraction displaying allelic DNA methylation where one allele is DNA methylated while the other allele is occupied by histone modifications H3K9me3 or H3K27me3. Our results show a mutually exclusive and complementary relationship between DNA methylation and H3K9me3 or H3K27me3. These results suggest that global DNA hypomethylation in breast cancer is tightly linked to the formation of repressive chromatin domains and gene silencing, thus identifying a potential epigenetic pathway for gene regulation in cancer cells and suggesting a possible new approach toward the development of cancer therapeutics. mRNA-Seq of polyA-selected RNA from breast cancer HCC1954 and normal breast HMEC. 36 cycles of sequencing on Illumina platform.

ORGANISM(S): Homo sapiens

SUBMITTER: Gary Hon

PROVIDER: E-GEOD-29119 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer.

Hon Gary C GC Hawkins R David RD Caballero Otavia L OL Lo Christine C Lister Ryan R Pelizzola Mattia M Valsesia Armand A Ye Zhen Z Kuan Samantha S Edsall Lee E LE Camargo Anamaria Aranha AA Stevenson Brian J BJ Ecker Joseph R JR Bafna Vineet V Strausberg Robert L RL Simpson Andrew J AJ Ren Bing B

Genome research 20111207 2

While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation of tumor suppressors, as well as changes in chromatin modifications as caused by genetic mutations of the chromatin-modifying machinery. However, the extent of epigenetic alterations in cancer cells has not been fully characterized. Here, we describe complete methylome maps at single nucleotide resolution of a low-passage breast cancer cell ...[more]

PMID: 22156296

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Project description:This is one of expressional parts of the study. These data were correlated to epigenetic marks and CG density of genes in analyzed cells. The whole study has a following summary: To elucidate possible roles of DNA methylation and chromatin marks in transcription, we performed epigenetic profiling of chromosome 19 in human bronchial epithelial cells (HBEC) and in the colorectal cancer cell line HCT116 as well as its counterpart with double knockout of DNMT1 and DNMT3B (HCT116-DKO). We found that H3K9me3 forms intragenic chromatin blocks along genes with low CpG density in the gene body. Analysis of H3K36me3 profiles indicated that this mark associates either with active genes with low CpG density and H3K9me3 in the gene body or with active genes with high CpG density and DNA hypermethylation in the gene body. In HCT116 cells with double knockout of DNMT1 and DNMT3B, transcription of genes with low CpG density in the gene body was highly elevated and associated with promoter DNA demethylation and rearrangement of H3K9me3 and H3K36me3 occupation. Our finding suggests that similar to DNA methylation, H3K9me3 may play a role in intragenic gene regulation. Further, we observed that a combination of low CpG density in gene bodies together with H3K9me3 and H3K36me3 marking is a specific epigenetic feature of zinc finger (ZNF) genes, which comprise 90% of all genes carrying both histone marks on chromosome 19. For high CpG density genes, transcription and H3K36me3 occupancy were not changed in condition of partial or intensive loss of DNA methylation in gene bodies in the HCT116-DKO cell line. siRNA experiments with SETD2 knockdown in both HBEC and HCT116-DKO cell lines failed to reduce DNA methylation in gene bodies under conditions of H3K36me3 depletion. Our study suggests that the H3K36me3 and DNA methylation marks in gene bodies are established independently from each other and points to similar functional roles of intragenic DNA methylation and intragenic H3K9me3 for CpG-rich and CpG-poor genes, respectively. Expression profile of human bronchial epithelia cells (HBEC) immortalized with hTERT and CDK4. To elucidate possible roles of DNA methylation and chromatin marks in transcription, we performed epigenetic profiling of chromosome 19 in human bronchial epithelial cells (HBEC) and analyzed gene expression by Affymetrix expression arrays in these cells. This is the expressional part of study.

Project description:This is one of expressional parts of the study. These data were correlated to epigenetic marks and CG density of genes in analyzed cells. The whole study has a following summary: To elucidate possible roles of DNA methylation and chromatin marks in transcription, we performed epigenetic profiling of chromosome 19 in human bronchial epithelial cells (HBEC) and in the colorectal cancer cell line HCT116 as well as its counterpart with double knockout of DNMT1 and DNMT3B (HCT116-DKO). We found that H3K9me3 forms intragenic chromatin blocks along genes with low CpG density in the gene body. Analysis of H3K36me3 profiles indicated that this mark associates either with active genes with low CpG density and H3K9me3 in the gene body or with active genes with high CpG density and DNA hypermethylation in the gene body. In HCT116 cells with double knockout of DNMT1 and DNMT3B, transcription of genes with low CpG density in the gene body was highly elevated and associated with promoter DNA demethylation and rearrangement of H3K9me3 and H3K36me3 occupation. Our finding suggests that similar to DNA methylation, H3K9me3 may play a role in intragenic gene regulation. Further, we observed that a combination of low CpG density in gene bodies together with H3K9me3 and H3K36me3 marking is a specific epigenetic feature of zinc finger (ZNF) genes, which comprise 90% of all genes carrying both histone marks on chromosome 19. For high CpG density genes, transcription and H3K36me3 occupancy were not changed in condition of partial or intensive loss of DNA methylation in gene bodies in the HCT116-DKO cell line. siRNA experiments with SETD2 knockdown in both HBEC and HCT116-DKO cell lines failed to reduce DNA methylation in gene bodies under conditions of H3K36me3 depletion. Our study suggests that the H3K36me3 and DNA methylation marks in gene bodies are established independently from each other and points to similar functional roles of intragenic DNA methylation and intragenic H3K9me3 for CpG-rich and CpG-poor genes, respectively. Expressional changes associated with SETD2 siRNA transfection in HBEC Compare siRNA vs. control

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Dataset Information

Gene expression analysis of breast cancer (HCC1954) and normal breast cells (HMEC)

Publications

Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer.

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