Genome-wide analysis of histone methylation reveals chromatin state-based regulation of host cellular gene expression induced by hepatitis B viruses
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Ni Bing
PROVIDER: E-GEOD-35465 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Hepatitis B virus (HBV) is a hepatotropic virus that can regulate many host cellular gene expressions participating in the HBV life cycle, liver inflammation and hepatocellular injury. However, the underlying mechanism of differential gene expression is not understood. We report here a genome-wide analysis of histone methylation on two histone H3 lysine residues (H3K4me3 and H3K27me3) and gene expression profiles in HepG2 and HepG2.2.15 cells. We found that specific correlation exists between gene expression and the amounts of H3K4me3 (positive correlation) and H3K27me3 (negative correlation) across the gene body. These correlations displayed three distinct modes (repressive, active and poised), reflecting different functions of these genes in the HBV life cycle, liver inflammation and hepatocellular injury. Furthermore, a permissive chromatin state of each gene was established by a combination of different histone modifications. Our findings reveal a complex regulation by histone methylation in differential gene expression and suggest that histone methylation may be responsible for the HBV life cycle, liver inflammation and hepatocellular injury induced by HBV. Examination of 2 different histone modifications (H3K4me3, H3K27me3) in 2 cell types (HepG2, HepG2.2.15).
2012-08-01 | E-GEOD-35462 | biostudies-arrayexpress
Project description:Hepatitis B virus (HBV) is a hepatotropic virus that can regulate many host cellular gene expressions participating in the HBV life cycle, liver inflammation and hepatocellular injury. However, the underlying mechanism of differential gene expression is not understood. We report here a genome-wide analysis of histone methylation on two histone H3 lysine residues (H3K4me3 and H3K27me3) and gene expression profiles in HepG2 and HepG2.2.15 cells. We found that specific correlation exists between gene expression and the amounts of H3K4me3 (positive correlation) and H3K27me3 (negative correlation) across the gene body. These correlations displayed three distinct modes (repressive, active and poised), reflecting different functions of these genes in the HBV life cycle, liver inflammation and hepatocellular injury. Furthermore, a permissive chromatin state of each gene was established by a combination of different histone modifications. Our findings reveal a complex regulation by histone methylation in differential gene expression and suggest that histone methylation may be responsible for the HBV life cycle, liver inflammation and hepatocellular injury induced by HBV. A large-scale analysis of gene expression of 2 different cell types (HepG2, HepG2.2.15) using a digital gene expression (DGE) tag profiling approach.
2012-08-01 | E-GEOD-35464 | biostudies-arrayexpress
Project description:H2B mono-ubiquitylation is required for multiple methylations of both H3K4 and H3K79 and has been implicated in gene expression from yeast to human. However, molecular crosstalk between H2BUb1 and other modifications, especially H3K4 and H3K79 methylations, remains unclear in vertebrates. To understand the functional role of H2BUb1, genome-wide histone modification patterns were measured in human cells. This study proposes dual roles of H2BUb1 that are both H3 methylation dependent and independent. First, H2BUb1 is a 5'-enriched active transcription mark and is co-occupied with H3K79 methylations in actively transcribed regions. Importantly, this study found a unique role of H2BUb1 in chromatin architecture independent of histone H3 methylations. H2BUb1 is well positioned in exon-intron boundaries of highly expressed exons and is specifically enriched in 5'-biased exons. Furthermore, H2BUb1 demonstrates increased occupancy in skipped exons compared to flanking exons for the human and mouse genome. Our findings suggest that a potentiating mechanism links H2BUb1 to both H3K79 methylations in actively transcribed regions and the exon-intron structure of highly expressed exons through the regulation of nucleosome dynamics during transcription elongation. We generated high-throughput sequencing (ChIP-seq) data for genome-wide occupancy of H2BUb1, nucleosome, H3K4me3, H3K36me3, H379me1/2/3, H3Ac, and mRNA in human embryonic carcinoma cells. We performed ChIP-seq for seven different histone modifications, MNase-seq, mRNA-seq (two replications), and inputDNA-seq in NCCIT cell lines (human embryonic carcinoma cell lines). We also performed mRNA-seq for RNF20-siRNA transfected NCCIT cells, where H2BUb1 signals decreased.
2012-03-07 | E-GEOD-25882 | biostudies-arrayexpress
Project description:We generated high-throughput sequencing (ChIP-seq) data for genome wide occupancy of hDot1L and RNAPII-5p in human embryonic carcinoma cell. Performing ChIP-seq for hDot1L and RNAPII-5p in NCCIT cell lines (embryonic carcinoma cell lines in human).
2012-09-27 | E-GEOD-26598 | biostudies-arrayexpress
Project description:The induction of pluripotency or trans-differentiation of one cell type to another can be accomplished with cell lineage-specific transcription factors. Here we report that repression of a single RNA binding protein PTB, which occurs during normal brain development via the action of miR-124, is sufficient to induce trans-differentiation of fibroblasts into functional neurons. Besides its traditional role in regulated splicing, we show that PTB has a previously undocumented function in the regulation of microRNA functions, suppressing or enhancing microRNA targeting by competitive binding on target mRNA or altering local RNA secondary structure. A key event during neuronal induction is the relief of PTB-mediated blockage of microRNA action on multiple components of the REST complex, thereby de-repressing a large array of neuronal genes, including miR-124 and multiple neuronal-specific transcription factors, in non-neuronal cells. This converts a negative feedback loop to a positive one to elicit cellular reprogramming to the neuronal lineage. Examination of PTB regulated AGO2/microRNA targeting in Hela cells by CLIP-seq (two biological replicates) , paired-end RNA-seq (control and PTB knockdown) and 3’end stability RNA-seq (control and PTB knockdown)
2013-01-17 | E-GEOD-42701 | biostudies-arrayexpress
Project description:Topoisomerases are crucial to solve DNA topological problems, but they have not been linked to RNA metabolism. Here we show that human topoisomerase 3M-NM-2 (Top3M-NM-2) is an RNA topoisomerase that biochemically and genetically interacts with FMRP, a protein deficient in Fragile X syndrome and known to regulate translation of mRNAs important for neuronal function and autism. Notably, the FMRP-Top3M-NM-2 interaction is abolished by a disease-associated FMRP mutation, and several human genetic studies link Top3M-NM-2 mutation to schizophrenia and intellectual disability. Top3M-NM-2 binds multiple mRNAs encoded by genes with neuronal functions related to schizophrenia and autism. Expression of one such gene, ptk2/FAK, is reduced in neuromuscular junctions of Top3M-NM-2 mutant flies. Synapse formation is defective in Top3M-NM-2 mutant flies and mice, as observed in FMRP mutant animals. Our findings suggest that Top3M-NM-2 acts as an RNA topoisomerase and works with FMRP to promote expression of mRNAs critical for neurodevelopment and mental health. We have identified Top3M-NM-2 as the first RNA topoisomerase in eukaryotes. To study whether Top3M-NM-2 binds mRNAs in vivo and also to identify its genome-wide RNA targets, we performed HITS-CLIP (high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation; Licatalosi et al. Nature 456, 464-469, 2008). In this method, proteins are covalently crosslinked with bound RNAs in vivo, thus allowing specific mapping of the sites of interaction of the protein with the RNA. We cultured a HeLa cells stably-expressing HF-Top3M-NM-2 and irradiated the cells with UV to crosslink RNA and proteins in vivo. Following cell lysis, RNA was partially digested using various concentrations of RNase A. The RNA crosslinked to HF-Top3M-NM-2 was then immunoprecipitated with anti-Flag M2 argarose beads (Sigma). As a control, we also performed a mock immunoprecipitation using HeLa cells that do not express HF-Top3M-NM-2. The 3M-bM-^@M-^Y ends of the purified RNAs were ligated to a p32-labeled RNA adapter, fractionated by SDS-PAGE, and transferred to a nitrocellulose membrane. The p32-labeled RNA-Top3M-NM-2 complexes were detected by autoradiography and recovered from the membrane. The complexes were treated with Proteinase K to remove proteins. The RNA was ligated at their 5M-bM-^@M-^Yend to another RNA adaptor, and reverse-transcribed to cDNA. The cDNA obtained was fractionated a denaturing 6% TBE-Urea gel (InVitrogen), amplified by PCR, and subjected to high-throughput sequencing by Genome Analyzer II (Illumina). Sequenced tags were mapped to the human genome (hg18, NCBI/NIH) and to human RefSeq genes using ELAND program (Illumina).
2013-08-04 | E-GEOD-47502 | biostudies-arrayexpress
Project description:The nuclear matrix associated hnRNP U/SAF-A protein has been implicated in diverse pathways from transcriptional regulation to telomere length control to X inactivation, but the precise mechanism underlying each of these processes has remained elusive. Here, we report hnRNP U as a regulator of SMN2 splicing from a custom RNAi screen. Genome-wide analysis by CLIP-seq reveals that hnRNP U binds virtually to all classes of regulatory non-coding RNAs, including all snRNAs required for splicing of both major and minor classes of introns, leading to the discovery that hnRNP U regulates U2 snRNP maturation and Cajal body morphology in the nucleus. Global analysis of hnRNP U-dependent splicing by RNA-seq coupled with bioinformatic analysis of associated splicing signals suggests a general rule for splice site selection through modulating the core splicing machinery. These findings exemplify hnRNP U/SAF-A as a potent regulator of nuclear ribonucleoprotein particles in diverse gene expression pathways. Examination of hnRNP U regulated splicing in Hela cells with CLIP-seq (two biological replicates) and paired-end RNA-seq (control and hnRNP U knockdown)
2012-02-16 | E-GEOD-34491 | biostudies-arrayexpress
Project description:In our study we applied a genome-wide DNA methylation analysis approach, MethylCap-seq, to map the differentially methylated regions in 24 tumor and matched normal colon samples. In total, 2687 frequently hypermethylated and 468 frequently hypomethylated regions were identified, which include potential biomarkers for CRC diagnosis. Hypermethylation in the tumor samples was enriched at CpG islands and gene promoters, while hypomethylation was distributed throughout the genome. Using epigenetic data from human embryonic stem cells, we show that frequent differentially methylated regions (DMRs) coincide with bivalent loci in human embryonic stem cells. DNA methylation is commonly thought to lead to cancer gene related silencing, however integration of publically available expression analysis shows that 75% of the frequently hypermethylation genes were most likely already lowly or not expressed in normal tissue. Collectively, our study provides genome-wide DNA methylation maps of colon cancer, comprehensive lists of DMRs, and gives further clues on the role of aberrant DNA methylation in CRC formation. To investigate DNA methylation in CRC in a genome-wide unbiased fashion, we applied MethylCap-seq. This method involves capture of methylated DNA using the MBD domain of MeCP2, and subsequent next-generation Illumina sequencing of eluted DNA. In addition, we compared MethylCap with RNA-seq and ChIP-seq profiles of H3K4me3 and H3K27me3 for the colon cancer tumor cell line HCT116 (HCT116 WT) and the cell line of HCT116 with DNMT1 and DNMT3b knockout (HCT116 DKO).
2012-10-26 | E-GEOD-39068 | biostudies-arrayexpress
Project description:To investigate global changes of miRNA profiles upon differentiation of human neural stem cells, we applied massively parallel sequencing (MPS) technology to an immortalized neural stem cell (HB1.F3) and its differentiated cell (F3.Olig2) lines. We identified 339 known miRNAs, out of which 170 miRNAs are up-regulated in F3.Olig2, while only 59 miRNAs in HB1.F3. We also identified 150 novel miRNA candidates. Sequencing miRNAs from an immortalized neural stem cell (HB1.F3) and its differentiated cell (F3.Olig2) lines
2013-05-23 | E-GEOD-15756 | biostudies-arrayexpress
Project description:Psoriasis and atopic dermatitis (AD) are characterized by polarized CD4+ T cell responses. During the polarization of naM-CM-/ve CD4+ T cells, DNA methylation plays an important role in the regulation of gene transcription. In this study, we profiled the genome-wide DNA methylation status of naM-CM-/ve CD4+ T cells in patients with psoriasis or AD and healthy controls using a ChIP-seq method. As a result, twenty-six regions in the genome ranging in size from 10 to 70 kb were markedly hypomethylated in patients with psoriasis. These regions were mostly pericentromeric on 10 different chromosomes and overlapped with various strong epigenomic signals, such as histone modifications and transcription factor binding sites, that were observed in the ENCODE project. Gene-centric analysis indicated that the promoter regions of 124 genes on the X chromosome had dramatically elevated methylation levels in patients with psoriasis as compared to those from healthy controls (> 4-fold). Moreover, immune-related genes on the X chromosome had higher hypermethylation than other genes (P < 0.05). These findings imply that methylation changes in naM-CM-/ve CD4+ T cells may affect CD4+ T cell polarization, especially in the pathogenesis of psoriasis. Keywords: Psoriasis, Atopic dermatitis, DNA methylation, naM-CM-/ve CD4+ T cells Sample submission examines DNA methylation from human naive CD4+ T cells in patients with psoriasis and atopic dermatitis. Note: Raw data available only for Sample GSM871288.
2012-03-17 | E-GEOD-35582 | biostudies-arrayexpress