Enhancers with tissue-specific activity are enriched in intronic regions
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB45744 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR6066810.fastq.gz | Fastqsanger.gz | |||
| ERR6066820.fastq.gz | Fastqsanger.gz | |||
| ERR6066811.fastq.gz | Fastqsanger.gz | |||
| ERR6066821.fastq.gz | Fastqsanger.gz | |||
| ERR6066812.fastq.gz | Fastqsanger.gz |
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Project description:Tissue function and homeostasis reflect the gene expression signature by which the combination of ubiquitous and tissue-specific genes contribute to the tissue maintenance and stimuli-responsive function. Enhancers are central to control this tissue-specific gene expression pattern. Here, we explore the correlation between the genomic location of enhancers and their role in tissue-specific gene expression. We find that enhancers showing tissue-specific activity are highly enriched in intronic regions and regulate the expression of genes involved in tissue-specific functions, whereas housekeeping genes are more often controlled by intergenic enhancers, common to many tissues. Notably, an intergenic-to-intronic active enhancers continuum is observed in the transition from developmental to adult stages: the most differentiated tissues present higher rates of intronic enhancers, whereas the lowest rates are observed in embryonic stem cells. Altogether, our results suggest that the genomic location of active enhancers is key for the tissue-specific control of gene expression.
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Project description:We have performed ChIP-seq of H3K27ac and H3K4me3 histone post-translational modifications at three stages during induced neural differentiation (ESCs, neural progenitors and neurons). This data has allowed us to identify candidate enhancer-like signatures in the genome, which we have defined as regions that are enriched in H3K27ac and depleted of H3K4me3.
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Project description:Determining the spatial and temporal activity patterns of enhancers remains a challenge in the functional annotation of the human genome. Here, we performed genome-wide mapping of tissue-specific in vivo binding sites for the enhancer-associated protein p300 and assessed in transgenic mice the utility of this information in identifying enhancers and predicting their activity patterns. Chromatin immunoprecipitation followed by massively-parallel sequencing was used to identify p300-enriched sites in mouse embryonic day 11.5 (e11.5) forebrain, midbrain, and limb. In total, 4,686 genomic regions were enriched for p300 in vivo in at least one of these tissues. To determine whether p300-binding accurately identifies enhancers and predicts their activity patterns, we tested 86 of these regions in a transgenic mouse enhancer assay at e11.5. In 88% of the cases, p300-enriched sequences were reproducible enhancers, and in 91% of these cases p300 enrichment correctly predicted the tissues in which in vivo activity was observed. Our results indicate that in vivo mapping of p300 binding to non-coding DNA is a highly effective means for identifying enhancers and their associated spatial activity patterns. Examination of p300 binding in 3 embryonic stage 11.5 mouse tissues
2009-02-11 | E-GEOD-13845 | biostudies-arrayexpress
Project description:The integrated activity of cis-regulatory elements fine-tunes transcriptional programs of mammalian cells by recruiting cell type–specific as well as ubiquitous transcription factors (TFs). Despite their key role in modulating transcription, enhancers are still poorly characterized at the molecular level, and their limited DNA sequence conservation in evolution and variable distance from target genes make their unbiased identification challenging. The coexistence of high mono-methylation and low tri-methylation levels of lysine 4 of histone H3 is considered a signature of enhancers, but a comprehensive view of histone modifications associated to enhancers is still lacking. By combining chromatin immunoprecipitation (ChIP) with mass spectrometry, we investigated cis-regulatory regions in macrophages to comprehensively identify histone marks specifically associated with enhancers, and to profile their dynamics after transcriptional activation elicited by an inflammatory stimulation. The intersection of the proteomics data with ChIP-seq and RNA-seq analyses revealed the existence of novel subpopulations of enhancers, marked by specific histone modification signatures: specifically, H3K36me2/K4me1 marks transcribed enhancers, while H3K36me3/K4me1 and H3K79me2/K4me1 combinations mark distinct classes of intronic enhancers. Thus, our MS analysis of functionally distinct genomic regions revealed the combinatorial code of histone modifications, highlighting the potential of proteomics in addressing fundamental questions in epigenetics.
2017-10-09 | PXD007582 | Pride
Project description:Determining the spatial and temporal activity patterns of enhancers remains a challenge in the functional annotation of the human genome. Here, we performed genome-wide mapping of tissue-specific in vivo binding sites for the enhancer-associated protein p300 and assessed in transgenic mice the utility of this information in identifying enhancers and predicting their activity patterns. Chromatin immunoprecipitation followed by massively-parallel sequencing was used to identify p300-enriched sites in mouse embryonic day 11.5 (e11.5) forebrain, midbrain, and limb. In total, 4,686 genomic regions were enriched for p300 in vivo in at least one of these tissues. To determine whether p300-binding accurately identifies enhancers and predicts their activity patterns, we tested 86 of these regions in a transgenic mouse enhancer assay at e11.5. In 88% of the cases, p300-enriched sequences were reproducible enhancers, and in 91% of these cases p300 enrichment correctly predicted the tissues in which in vivo activity was observed. Our results indicate that in vivo mapping of p300 binding to non-coding DNA is a highly effective means for identifying enhancers and their associated spatial activity patterns.
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2024-06-10 | GSE247393 | GEO
Project description:We used genome-wide sequencing methods to study stimulus-dependent enhancer function in neurons. We identified ~12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Remarkably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 that is mono-methylated at lysine 4 (H3K4me1). The level of eRNA expression at neuronal enhancers positively correlates with the level of mRNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis. Examination of genome-wide binding of three types of modified histones, four transcription factors, and RNA polymerase II (ChIP-Seq), as well as RNA expression (RNA-Seq) before and after membrane depolarization via application of extracellular potassium.
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Project description:In this study, we explored the in vivo expression dynamics of tissue-specific non-coding RNAs in embryonic mouse tissues via in-depth transcriptome profiling. Overall, approximately 80% of validated in vivo enhancers show tissue-specific RNA expression that correlates with tissue-specific enhancer activity. Globally, we identified thousands of tissue-specifically transcribed non-coding regions (TSTRs) displaying various genomic hallmarks of bona fide enhancers. Together, our results demonstrate that tissue-specific eRNA expression is a common feature of in vivo enhancers, as well as a major source of extragenic transcription, and that eRNA expression signatures can be used to predict tissue-specific enhancers independent of known epigenomic enhancer marks. Examimation of total RNA expression in mouse heart and limb tissues collected at mouse embryonic day 11.5.
2014-09-11 | E-GEOD-58157 | biostudies-arrayexpress
Project description:It has been postulated that noncoding RNAs (ncRNAs) are involved in the post-transcriptional control of gene expression, and may have contributed to the emergence of the complex attributes observed in mammalians. The complement of ncRNAs expressed from intronic regions of the human and mouse genomes comprises at least 78,147 and 39,660 transcriptional units, respectively. To identify conserved intronic sequences expressed in both humans and mice, we used custom-designed human cDNA microarrays to separately interrogate RNA from mouse and human liver, kidney and prostate tissues. An overlapping tissue expression signature was detected for both species, comprising 198 transcripts; among these, twenty two RNAs map to intronic regions with evidence of evolutionary conservation in humans and mice. Transcription of selected human-mouse intronic ncRNAs was confirmed using strand specific RT-PCR. Altogether, these results support an evolutionarily conserved role of intronic ncRNAs in human and mouse, which are likely to be involved in the fine tuning of gene expression regulation in different mammalian tissues. Keywords: tissue expression pattern
2008-06-01 | GSE9950 | GEO
Project description:It has been postulated that noncoding RNAs (ncRNAs) are involved in the post-transcriptional control of gene expression, and may have contributed to the emergence of the complex attributes observed in mammalians. The complement of ncRNAs expressed from intronic regions of the human and mouse genomes comprises at least 78,147 and 39,660 transcriptional units, respectively. To identify conserved intronic sequences expressed in both humans and mice, we used custom-designed human cDNA microarrays to separately interrogate RNA from mouse and human liver, kidney and prostate tissues. An overlapping tissue expression signature was detected for both species, comprising 198 transcripts; among these, twenty two RNAs map to intronic regions with evidence of evolutionary conservation in humans and mice. Transcription of selected human-mouse intronic ncRNAs was confirmed using strand specific RT-PCR. Altogether, these results support an evolutionarily conserved role of intronic ncRNAs in human and mouse, which are likely to be involved in the fine tuning of gene expression regulation in different mammalian tissues. Keywords: tissue expression pattern 1. Experiment Design: 1.1. Type of experiment: The experiments described here aim to generate expression profiles from human and mouse prostate, kidney and liver tissue samples using a custom-designed cDNA microarray platform with 4,608 unique elements in replicate (9,216) enriched in gene fragments that map to intronic regions of known human genes. The platform consists of 3,355 probes of human cDNA fragments that map in the human genome sequence either to intronic regions of known genes (822), to unannotated regions of the human genome (241) or to known exons of RefSeq genes (2,292). We separately compared the expression profiles obtained from human and mouse samples to identify sequence conserved tissue-specific intronic transcripts. 1.2. Experimental factors: Tissues from liver, prostate and kidney from five adult male mice of the Balb/c strain were obtained and frozen in liquid nitrogen. Likewise, five non-tumor samples of human prostate, kidney or liver from our tumor bank were selected. All samples were obtained from patients who signed informed consent, and approval was received from the ethics committees of the hospitals. Total RNA was purified from tissues and treated with DNAse to reduce the levels of genomic DNA contaminant. Either human and or mouse samples from for each tissue from the five individuals were separately pooled using equal quantities of RNA. 1.3. The number of hybridizations performed in the experiment. RNA pools from each tissue sample was hybridized twice, performing a total of 18 hybridizations. 1.4. The type of reference used for the hybridizations, if any. All hybridizations included external mRNA spikes for quality control of the experiments (detailed below in section 2.5). Hybridizations were performed as single color experiments. 1.5. Hybridization design: Three aliquots of 15ug of the pool of total RNA from each tissue was labeled with Cy5-dUTP after reverse transcription (CyScribe first strand cDNA labeling kit, Amershan Biosciences) and hybridizations were carried out using all labeled-target in an Automate Slide Processor (Amershan Biosciences). Images were obtained using a Generation III Scanner (Amersham Biosciences). The human and mouse obtained expression data were independently analyzed using a highly stringent methodology, including different statistical approaches (see below for a detailed description). 1.6. Quality control steps taken: Integrity of total RNA was checked by electrophoresis using the Bio Sizing total RNA Nano assay in the 2100 Bioanalyzer (Agilent Technologies). Three replicates of each experiment were performed, as describe in the previous section.
2008-06-01 | E-GEOD-9950 | biostudies-arrayexpress