Similar Datasets
Project description:The inverse correlation between DNA methylation and steady state mRNA levels is imperfect; a large number of genes, which are unmethylated in the promoter region, are silenced. We show here that either pharmacological inhibition of DNA methyltransferase (DNMT1) with 5-aza-2'-deoxycytidine (5-azaCdR) or knockdown with shRNA dramatically expands the number of transcription initiation positions in the genome including many unmethylated promoters. Induction of unmethylated promoters in response to inhibition of DNMT1 is a result of activation by demethylation of methylated upstream regulators such as the transcription factor HNF4A. Our results imply that the landscape of genes that are regulated by DNA methylation is more wide-ranging than genes silenced by methylation of their own cis regulatory sequences. We propose a hierarchical model of transcriptional control by DNA methylation whereby regulation of unmethylated promoters is dependent on the methylation state of trans upstream regulators.
2025-07-13 | GSE85312 | GEO
Project description:The inverse correlation between DNA methylation and steady state mRNA levels is imperfect; a large number of genes, which are unmethylated in the promoter region, are silenced. We show here that either pharmacological inhibition of DNA methyltransferase (DNMT1) with 5-aza-2'-deoxycytidine (5-azaCdR) or knockdown with shRNA dramatically expands the number of transcription initiation positions in the genome including many unmethylated promoters. Induction of unmethylated promoters in response to inhibition of DNMT1 is a result of activation by demethylation of methylated upstream regulators such as the transcription factor HNF4A. Our results imply that the landscape of genes that are regulated by DNA methylation is more wide-ranging than genes silenced by methylation of their own cis regulatory sequences. We propose a hierarchical model of transcriptional control by DNA methylation whereby regulation of unmethylated promoters is dependent on the methylation state of trans upstream regulators.
2025-07-13 | GSE85376 | GEO
Project description:The inverse correlation between DNA methylation and steady state mRNA levels is imperfect; a large number of genes, which are unmethylated in the promoter region, are silenced. We show here that either pharmacological inhibition of DNA methyltransferase (DNMT1) with 5-aza-2'-deoxycytidine (5-azaCdR) or knockdown with shRNA dramatically expands the number of transcription initiation positions in the genome including many unmethylated promoters. Induction of unmethylated promoters in response to inhibition of DNMT1 is a result of activation by demethylation of methylated upstream regulators such as the transcription factor HNF4A. Our results imply that the landscape of genes that are regulated by DNA methylation is more wide-ranging than genes silenced by methylation of their own cis regulatory sequences. We propose a hierarchical model of transcriptional control by DNA methylation whereby regulation of unmethylated promoters is dependent on the methylation state of trans upstream regulators.
2025-07-13 | GSE85313 | GEO
Project description:DNA methylation controls unmethylated transcription start sites in the genome in trans
| PRJNA338155 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-09-01 | GSE60658 | GEO
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.
| S-EPMC3691241 | biostudies-literature
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.
| S-EPMC6522544 | biostudies-literature
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: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.
| S-EPMC3502543 | biostudies-literature
Project description:It is likely that evolutionary differences among species are driven by sequence changes in regulatory regions. Likewise, polymorphisms in the promoter regions may be responsible for interindividual differences at the level of populations. We present an unbiased survey of genetic variation in 2-kb segments upstream of the transcription start sites of 28 protein-coding genes, characterized in five population groups of different geographic origin. On average, we found 9.1 polymorphisms and 8.8 haplotypes per segment with corresponding nucleotide and haplotype diversities of 0.082% and 58%, respectively. We characterized these segments through different summary statistics, Hardy-Weinberg equilibria fixation index (Fst) estimates, and neutrality tests, as well as by analyzing the distributions of haplotype allelic classes, introduced here to assess the departure from neutrality and examined by coalescent simulations under a simple population model, assuming recombinations or different demography. Our results suggest that genetic diversity in some of these regions could have been shaped by purifying selection and driven by adaptive changes in the other, thus explaining the relatively large variance in the corresponding genetic diversity indices loci. However, some of these effects could be also due to linkage with surrounding sequences, and the neutralists' explanations cannot be ruled out given uncertainty in the underlying demographic histories and the possibility of random effects due to the small size of the studied segments.
| S-EPMC2683062 | biostudies-literature