Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Nanoscale Chromatin Profiling of Gastric Adenocarcinoma

ABSTRACT: To identify chromatin alterations in primary gastric adenocarcionomas, we performed nano-scale chromatin immunoprecipitation-sequencing (Nano-CHiPseq) of histone modifications in 5 gastric cancers and matched normal tissues, We identified hundreds of somatically-altered promoters (marked by H3K4me3) and enhancers (H3K4me1). The majority of cancer-associated promoters localized to genomic sites lacking previously-annotated transcription start sites (“cryptic promoters”), driving high expression of nearby genes implicated in gastrointestinal cancers, embryonic development, and tissue specification. Our findings demonstrate the feasibility of performing chromatin profiling on solid tumors where tissue is limiting, to identify in non-coding regions regulatory elements, transcriptional patterns and genetic variants associated with cancer. We propose a pervasive role for cryptic promoters in the reactivation of early developmental programs in gastric cancer, and the potential utility of cryptic promoters as biomarkers of malignancy. Five gastric cancer tumor normal pairs are profiling in multiple number of chromatin marks

ORGANISM(S): Homo sapiens

SUBMITTER: Niantao Deng

PROVIDER: E-GEOD-51776 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements.

Muratani Masafumi M Deng Niantao N Ooi Wen Fong WF Lin Suling Joyce SJ Xing Manjie M Xu Chang C Qamra Aditi A Tay Su Ting ST Malik Simeen S Wu Jeanie J Lee Ming Hui MH Zhang Shenli S Tan Luke Lin Chuen LL Chua Huihoon H Wong Wai Keong WK Ong Hock Soo HS Ooi London Lucien LL Chow Pierce Kah-How PK Chan Weng Hoong WH Soo Khee Chee KC Goh Liang Kee LK Rozen Steve S Teh Bin Tean BT Yu Qiang Q Ng Huck Hui HH Tan Patrick P

Nature communications 20140710

Chromatin alterations are fundamental hallmarks of cancer. To study chromatin alterations in primary gastric adenocarcinomas, we perform nanoscale chromatin immunoprecipitation sequencing of multiple histone modifications in five gastric cancers and matched normal tissues. We identify hundreds of somatically altered promoters and predicted enhancers. Many cancer-associated promoters localize to genomic sites lacking previously annotated transcription start sites (cryptic promoters), driving expr ...[more]

PMID: 25008978

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Project description:Dramatic changes of gene expressions are known to occur in human endometrial stromal cells (ESC) during decidualization. The changes in gene expression are associated with changes of chromatin structure, which are regulated by epigenetic mechanisms such as histone modifications. Here, we investigated genome-wide changes in histone modifications and mRNA expressions associated with decidualization in human ESC using chromatin immunoprecipitation (ChIP) combined with next-generation sequencing. ESC were incubated with estradiol and medroxyprogesterone acetate for 14 days to induce decidualization. The ChIP-sequence data showed that induction of decidualization increased H3K27ac and H3K4me3 signals in many genomic regions but decreased in only a few regions. Most (80%) of the H3K27ac-increased regions and half of the H3K4me3-increased regions were located in the distal promoter regions (more than 3 kb upstream or downstream of the transcription start site). RNA-sequence showed that induction of decidualization up-regulated 881 genes, 223 of which had H3K27ac- or H3K4me3-increased regions in the proximal and distal promoter regions. Induction of decidualization increased the mRNA levels of these genes more than it increased the mRNA levels of genes without H3K27ac- or H3K4me3-increased regions. Pathway analysis revealed that up-regulated genes with the H3K27ac- or H3K4me3-increased regions were associated with insulin signaling. These results show that histone modification statuses genome-widely change in human ESC by induction of decidualization. The main changes of histone modifications are increases of H3K27ac and H3K4me3 in both the proximal and distal promoter regions, which are involved in the up-regulation of gene expression that occurs during decidualization. Examination of 4 different histone modifications in human endometrial stromal cells with or without EP inductions for 2 individuals. (EP induction: induction with estradiol (10-8 M) and medroxyprogesterone acetate (10-6 M))

Dataset Information

Nanoscale Chromatin Profiling of Gastric Adenocarcinoma

Publications

Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements.

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