Genome-wide identification of transcribed enhancer candidates during pattern triggered immunity in Arabidopsis
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ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE181721 | GEO | 2022/06/21
REPOSITORIES: GEO
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Project description:In this study, we used Global Run-On sequencing (GRO-seq), a method that assays the genome-wide location and orientation of all active RNA polymerases. We generated a global profile of active transcription at ERM-NM-1 binding sites in MCF-7 human breast cancer cells in response to short time course of E2 treatment. This method enabled us to detect active transcription at enhancers and define a class of primary transcripts transcribed uni- or bidirectionally from the ERM-NM-1 binding sites. The raw data used in this study is from GSE27463 but sequenced to a greater depth. Using GRO-seq over a time course (0, 10, 40 min) of estrogen signaling in ER-alpha positive MCF-7 human breast cancer cells.
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Project description:In this study, we used Global Run-On sequencing (GRO-seq), a method that assays the genome-wide location and orientation of all active RNA polymerases. We generated a global profile of active transcription at ERα binding sites in MCF-7 human breast cancer cells in response to short time course of E2 treatment. This method enabled us to detect active transcription at enhancers and define a class of primary transcripts transcribed uni- or bidirectionally from the ERα binding sites. The raw data used in this study is from GSE27463 but sequenced to a greater depth.
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Project description:<p>Non-coding elements in our genomes that play critical roles in complex disease are frequently marked by highly unstable RNA species. Sequencing nascent RNAs attached to an actively transcribing RNA polymerase complex can identify unstable RNAs, including those templated from gene-distal enhancers (eRNAs). However, nascent RNA sequencing techniques remain challenging to apply in some cell lines and especially to intact tissues, limiting broad applications in fields such as cancer genomics and personalized medicine. Here we report the development of chromatin run-on and sequencing (ChRO-seq), a novel run-on technology that maps the location of RNA polymerase using virtually any frozen tissue sample, including samples with degraded RNA that are intractable to conventional RNA-seq. We used ChRO-seq to develop the first maps of nascent transcription in 23 human glioblastoma (GBM) brain tumors and patient derived xenografts. Remarkably, >90,000 distal enhancers discovered using the signature of eRNA biogenesis within primary GBMs closely resemble those found in the normal human brain, and diverge substantially from GBM cell models. Despite extensive overall similarity, 12% of enhancers in each GBM distinguish normal and malignant brain tissue. These enhancers drive regulatory programs similar to the developing nervous system and are enriched for transcription factor binding sites that specify a stem-like cell fate. These results demonstrate that GBMs largely retain the enhancer landscape associated with their tissue of origin, but selectively adopt regulatory programs that are responsible for driving stem-like cell properties. We also identified enhancers and their associated transcription factors that regulate genes characteristic of each known GBM subtype, and discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study uncovers new insights into the molecular etiology of GBM and introduces ChRO-seq which can now be used to map regulatory programs contributing to a variety of complex diseases.</p>
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Project description:Estrogen receptor alpha (ERα) signaling mainly occupies on distal enhancers within genome and plays an essential role in ERα-positive breast cancer. ERα usually requires co-factors to regulate the enhancer activity. By analysis of genome-wide nascent transcript profiling in breast cancer cells, we identified a special group of eRNAs that are functionally important for estrogen-induced transcriptional repression. In addition to stabilizing promoter-enhancer looping structure, these eRNAs recruit ERα to particular enhancers of target genes, facilitate the hierarchical formation of a functional transcriptional complex, and cause gene silencing. Interestingly, we found that ERα directly binds to eRNAs and its DNA-binding domain mediates the interaction with RNA molecules. Our ChIP-seq data in MCF-7 cells indicating that ERαwas not able to bind to E2-activated enhancers, which is consistent with the DNA-binding function reported before; moreover the DBD-truncated ERα was not able to bind to E2-repressed enhancers as well, which further supports our hypothesis that eRNA from E2-repressed enhancers help to recruit ERα to specific enhancers through the interaction with DBD domain. Substitution of ERα-DDBD showed a global effect on both induction and repression of ERα target genes as examined by RNA-seq. Further, these eRNAs help with the formation of a specific ERα-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses transcription of target genes. Our work demonstrated that eRNAs, as a distinctive class of cis-acting molecules besides chromatin regulatory elements, play an important role in modulating and refining locus-specific transcriptional program.
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Project description:Estrogen receptor alpha (ERα) signaling mainly occupies on distal enhancers within genome and plays an essential role in ERα-positive breast cancer. ERα usually requires co-factors to regulate the enhancer activity. By analysis of genome-wide nascent transcript profiling in breast cancer cells, we identified a special group of eRNAs that are functionally important for estrogen-induced transcriptional repression. In addition to stabilizing promoter-enhancer looping structure, these eRNAs recruit ERα to particular enhancers of target genes, facilitate the hierarchical formation of a functional transcriptional complex, and cause gene silencing. Interestingly, we found that ERα directly binds to eRNAs and its DNA-binding domain mediates the interaction with RNA molecules. Our ChIP-seq data in MCF-7 cells indicating that ERαwas not able to bind to E2-activated enhancers, which is consistent with the DNA-binding function reported before; moreover the DBD-truncated ERα was not able to bind to E2-repressed enhancers as well, which further supports our hypothesis that eRNA from E2-repressed enhancers help to recruit ERα to specific enhancers through the interaction with DBD domain. Substitution of ERα-DDBD showed a global effect on both induction and repression of ERα target genes as examined by RNA-seq. Further, these eRNAs help with the formation of a specific ERα-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses transcription of target genes. Our work demonstrated that eRNAs, as a distinctive class of cis-acting molecules besides chromatin regulatory elements, play an important role in modulating and refining locus-specific transcriptional program.
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Project description:Gene regulatory programs in different cell types are largely defined through cell-specific enhancers activity. The histone variant H2A.Z has been shown to play important roles in transcription mainly by controlling proximal promoters, but its effect on enhancer functions remains unclear. Here, we demonstrate by genome-wide approaches that H2A.Z is present at a subset of active enhancers bound by the estrogen receptor alpha (ERα). We also determine that H2A.Z does not influence the local nucleosome positioning around ERα-enhancers using ChIP-sequencing at nucleosomal resolution and unsupervised pattern discovery. We further highlight that H2A.Z-enriched enhancers are associated with chromatin accessibility, H3K122ac enrichment and hypomethylated DNA. Moreover, upon estrogen stimulation, the enhancers occupied by H2A.Z produce enhancer RNAs (eRNAs), and recruit RNA polymerase II as well as RAD21, a member of the cohesin complex involved in chromatin interactions between enhancers and promoters. Importantly, their recruitment and eRNAs production are abolished by H2A.Z depletion, thereby revealing a novel functional link between H2A.Z occupancy and enhancer activity. Taken together, our findings suggest that H2A.Z acts as an important player for enhancer functions by establishing and maintaining a chromatin environment required for RNA polymerase II recruitment, eRNAs transcription and enhancer-promoters interactions, all essential attributes of enhancer activity. The MNase ChIP-seqs in this study measure the genome-wide binding landscape of H2A.Z, H3K4me1, H3K27ac and H3K4me3 in MCF-7 cells in the absence or presence of E2. Two biological replicates were done for each ChIP-seq experiment and for each condition, as well as, control input.
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