DNA methylation at transcription start sites blocks TBP binding and transcription onset by RNApolII
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE60658 | GEO | 2015/09/01
SECONDARY ACCESSION(S): PRJNA259204
REPOSITORIES: GEO
Similar Datasets
Project description:We measured the methylation levels of gene promoters of cerebral cortex of mice. We used MeDIP-array, immunoprecipitating genomic DNA with an antibody against methylated DNA and measuring methylation levels using custom arrays. The input DNA was used as control.
2015-09-01 | GSE60656 | GEO
Project description:We report the application of ChIP bisulfite sequencing (ChIPbisSeq) to establish the methylation state of DNA bound to RNApol2 phosphorylated in Ser5 (RNAPol2Ser5) in the mouse cortex. We first profiled the RNAPol2Ser5 binding using regular ChIPSeq from 45 million raw read pairs (31 million unique pairs were aligned to the genome). Then we used bisulfite converted DNA immunoprecipitated with an antibody against RNAPol2Ser5 (87 million raw read pairs, 38 million unique read pairs aligned to the genome) to map RNAPol2Ser5 sites and to establish the methylation state at these sites.
2015-09-01 | GSE60657 | GEO
Project description:We measured the methylation levels of gene promoters of cerebral cortex of mice. We used MeDIP-array, immunoprecipitating genomic DNA with an antibody against methylated DNA and measuring methylation levels using custom arrays. The input DNA was used as control. triplicates of frontal cortex DNA pools of 3 mice
2015-09-01 | E-GEOD-60656 | biostudies-arrayexpress
Project description:We report the application of ChIP bisulfite sequencing (ChIPbisSeq) to establish the methylation state of DNA bound to RNApol2 phosphorylated in Ser5 (RNAPol2Ser5) in the mouse cortex. We first profiled the RNAPol2Ser5 binding using regular ChIPSeq from 45 million raw read pairs (31 million unique pairs were aligned to the genome). Then we used bisulfite converted DNA immunoprecipitated with an antibody against RNAPol2Ser5 (87 million raw read pairs, 38 million unique read pairs aligned to the genome) to map RNAPol2Ser5 sites and to establish the methylation state at these sites. Examination of methylation state at RNAPol2Ser5 binding sites in the mouse cortex.
2015-09-01 | E-GEOD-60657 | biostudies-arrayexpress
Project description:DNA methylation at transcription start sites blocks TBP binding and transcription onset by RNApolII
| PRJNA259204 | ENA
Project description:Despite almost 40 years of molecular genetics research in Escherichia coli a major fraction of its Transcription Start Sites (TSSs) are still unknown, limiting therefore our understanding of the regulatory circuits that control gene expression in this model organism. RegulonDB (http://regulondb.ccg.unam.mx/) is aimed at integrating the genetic regulatory network of E. coli K12 as an entirely bioinformatic project up till now. In this work, we extended its aims by generating experimental data at a genome scale on TSSs, promoters and regulatory regions. We implemented a modified 5' RACE protocol and an unbiased High Throughput Pyrosequencing Strategy (HTPS) that allowed us to map more than 1700 TSSs with high precision. From this collection, about 230 corresponded to previously reported TSSs, which helped us to benchmark both our methodologies and the accuracy of the previous mapping experiments. The other ca 1500 TSSs mapped belong to about 1000 different genes, many of them with no assigned function. We identified promoter sequences and type of sigma factors that control the expression of about 80% of these genes. As expected, the housekeeping sigma(70) was the most common type of promoter, followed by sigma(38). The majority of the putative TSSs were located between 20 to 40 nucleotides from the translational start site. Putative regulatory binding sites for transcription factors were detected upstream of many TSSs. For a few transcripts, riboswitches and small RNAs were found. Several genes also had additional TSSs within the coding region. Unexpectedly, the HTPS experiments revealed extensive antisense transcription, probably for regulatory functions. The new information in RegulonDB, now with more than 2400 experimentally determined TSSs, strengthens the accuracy of promoter prediction, operon structure, and regulatory networks and provides valuable new information that will facilitate the understanding from a global perspective the complex and intricate regulatory network that operates in E. coli.
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Project description:Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility genes. Regulatory sequences at DPP10 and additional loci carried a strong footprint of hominid adaptation, including elevated nucleotide substitution rates and regulatory motifs absent in other primates (including archaic hominins), with evidence for selective pressures during more recent evolution and adaptive fixations in modern populations. Chromosome conformation capture at two neurodevelopmental disease loci, 2q14.1 and 16p11.2, revealed higher order chromatin structures resulting in physical contact of multiple human-specific H3K4me3 peaks spaced 0.5-1 Mb apart, in conjunction with a novel cis-bound antisense RNA linked to Polycomb repressor proteins and downregulated DPP10 expression. Therefore, coordinated epigenetic regulation via newly derived TSS chromatin could play an important role in the emergence of human-specific gene expression networks in brain that contribute to cognitive functions and neurological disease susceptibility in modern day humans.
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Project description:Predicting the transcription start sites (TSSs) of microRNAs (miRNAs) is important for understanding how these small RNA molecules, known to regulate translation and stability of protein-coding genes, are regulated themselves. Previous approaches are primarily based on genetic features, trained on TSSs of protein-coding genes, and have low prediction accuracy. Recently, a support vector machine based technique has been proposed for miRNA TSS prediction that uses known miRNA TSS for training the classifier along with a set of existing and novel CpG island based features. Current progress in epigenetics research has provided genomewide and tissue-specific reports about various phenotypic traits. We hypothesize that incorporating epigenetic characteristics into statistical models may lead to better prediction of primary transcripts of human miRNAs. In this paper, we have tested our hypothesis on brain-specific miRNAs by using epigenetic as well as genetic features to predict the primary transcripts. For this, we have used a sophisticated feature selection technique and a robust classification model. Our prediction model achieves an accuracy of more than 80% and establishes the potential of epigenetic analysis for in silico prediction of TSSs.
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Project description:Although promoter-associated CpG islands have been established as targets of DNA methylation changes in cancer, previous studies suggest that epigenetic dysregulation outside the promoter region may be more closely associated with transcriptional changes. Here we examine DNA methylation, chromatin marks, and transcriptional alterations to define the relationship between transcriptional modulation and spatial changes in chromatin structure. Using human papillomavirus-related oropharyngeal carcinoma as a model, we show aberrant enrichment of repressive H3K9me3 at the transcriptional start site (TSS) with methylation-associated, tumor-specific gene silencing. Further analysis identifies a hypermethylated subtype which shows a functional convergence on MYC targets and association with CREBBP/EP300 mutation. The tumor-specific shift to transcriptional repression associated with DNA methylation at TSSs was confirmed in multiple tumor types. Our data may show a common underlying epigenetic dysregulation in cancer associated with broad enrichment of repressive chromatin marks and aberrant DNA hypermethylation at TSSs in combination with MYC network activation.
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Project description:Progression of RNA polymerase II (RNAPII) transcription relies on the appropriately positioned activities of elongation factors. The resulting profile of factors and chromatin signatures along transcription units provides a "positional information system" for transcribing RNAPII. Here, we investigate a chromatin-based mechanism that suppresses intragenic initiation of RNAPII transcription. We demonstrate that RNAPII transcription across gene promoters represses their function in plants. This repression is characterized by reduced promoter-specific molecular signatures and increased molecular signatures associated with RNAPII elongation. The conserved FACT histone chaperone complex is required for this repression mechanism. Genome-wide Transcription Start Site (TSS) mapping reveals thousands of discrete intragenic TSS positions in fact mutants, including downstream promoters that initiate alternative transcript isoforms. We find that histone H3 lysine 4 mono-methylation (H3K4me1), an Arabidopsis RNAPII elongation signature, is enriched at FACT-repressed intragenic TSSs. Our analyses suggest that FACT is required to repress intragenic TSSs at positions that are in part characterized by elevated H3K4me1 levels. In sum, conserved and plant-specific chromatin features correlate with the co-transcriptional repression of intragenic TSSs. Our insights into TSS repression by RNAPII transcription promise to inform the regulation of alternative transcript isoforms and the characterization of gene regulation through the act of pervasive transcription across eukaryotic genomes.
| S-EPMC6373976 | biostudies-literature