Similar Datasets
Project description:DNA methylation is one of the most important epigenetic marks and changes in DNA methylation patterns have been associated with many different types of cancer. Recently, three-dimensional (3D) genome organisation has been demonstrated to play a fundamental role in gene regulation. Determining the interplay between DNA methylation and 3D chromatin structure and function is challenging due to the extreme complexity of epigenetic regulation. To study the impact of DNA methylation on 3D genome organization, we performed a time-course of Decitabine treatment in tamoxifen-resistant MCF7 (TAMR) cells. Decitabine was applied daily for 7 days, followed by “recovery” up to 28 days and DNA methylation (EPIC), gene expression (RNA-seq) and promoter-enhancer interactions (PCHi-C) were assessed on day 7 post-Decitabine- and Vehicle-treatment and day 28 “Recovery” and Vehicle treatment in duplicate. Our data revealed a functional link between DNA hypomethylation at distal enhancer regions, enhancer-promoter interactions, and gene regulation.
2023-08-07 | GSE216986 | GEO
Project description:DNA methylation is one of the most important epigenetic marks and changes in DNA methylation patterns have been associated with many different types of cancer. Recently, three-dimensional (3D) genome organisation has been demonstrated to play a fundamental role in gene regulation. Determining the interplay between DNA methylation and 3D chromatin structure and function is challenging due to the extreme complexity of epigenetic regulation. To study the impact of DNA methylation on 3D genome organization, we performed a time-course of Decitabine treatment in tamoxifen-resistant MCF7 (TAMR) cells. Decitabine was applied daily for 7 days, followed by “recovery” up to 28 days and DNA methylation (EPIC), gene expression (RNA-seq) and promoter-enhancer interactions (PCHi-C) were assessed on day 7 post-Decitabine- and Vehicle-treatment and day 28 “Recovery” and Vehicle treatment in duplicate. Our data revealed a functional link between DNA hypomethylation at distal enhancer regions, enhancer-promoter interactions, and gene regulation.
2023-08-08 | GSE216988 | GEO
Project description:DNA methylation is one of the most important epigenetic marks and changes in DNA methylation patterns have been associated with many different types of cancer. Recently, three-dimensional (3D) genome organisation has been demonstrated to play a fundamental role in gene regulation. Determining the interplay between DNA methylation and 3D chromatin structure and function is challenging due to the extreme complexity of epigenetic regulation. To study the impact of DNA methylation on 3D genome organization, we performed a time-course of Decitabine treatment in tamoxifen-resistant MCF7 (TAMR) cells. Decitabine was applied daily for 7 days, followed by “recovery” up to 28 days and DNA methylation (EPIC), gene expression (RNA-seq) and promoter-enhancer interactions (PCHi-C) were assessed on day 7 post-Decitabine- and Vehicle-treatment and day 28 “Recovery” and Vehicle treatment in duplicate. Our data revealed a functional link between DNA hypomethylation at distal enhancer regions, enhancer-promoter interactions, and gene regulation.
2023-08-08 | GSE216987 | GEO
Project description:Recent studies have revealed an unexpected role of DNA methylation at promoter regions in transcription activation. However, whether DNA methylation at enhancer regions activates gene expression and influences cellular functions remains to be determined. In this study, by employing the transcription factor krÜppel-like factor 4 (KLF4) that binds to methylated CpGs (mCpGs), we investigated the molecular outcomes of the recruitment of KLF4 to mCpGs at enhancer regions in human glioblastoma cells. First, by integrating KLF4 ChIP-seq, whole-genome bisulfite sequence, and H3K27ac ChIP-seq datasets, we found 1,299 highly methylated (β >0.5) KLF4 binding sites, three-quarters of which were located at putative enhancer regions, including gene bodies and intergenic regions. In the meantime, by proteomics, we identified 16 proteins as putative targets upregulated by KLF4-mCpG binding at enhancer regions. By chromosome conformation capture (3C) analysis, we demonstrated that KLF4 bound to methylated CpGs at the enhancer regions of the B-cell lymphocyte kinase (BLK) and Lim domain only protein 7 (LMO7) genes, and activated their expression via 3D chromatin loop formation with their promoter regions. Expression of mutant KLF4, which lacks KLF4 ability to bind methylated DNA, or removal of DNA methylation in enhancer regions by a DNA methyltransferase inhibitor abolished chromatin loop formation and gene expression, suggesting the essential role of DNA methylation in enhancer-promoter interactions. Finally, we performed functional assays and showed that BLK was involved in glioblastoma cell migration. Together, our study established the concept that DNA methylation at enhancer regions interacts with transcription factors to activate gene expression and influence cellular functions.
| S-EPMC6224223 | biostudies-literature
Project description:Recent experimental and computational efforts have provided large data sets describing three-dimensional organization of mouse and human genomes and showed the interconnection between the expression profile, epigenetic state, and spatial interactions of loci. These interconnections were utilized to infer the spatial organization of chromatin, including enhancer-promoter contacts, from one-dimensional epigenetic marks. Here, we show that the predictive power of some of these algorithms is overestimated due to peculiar properties of the biological data. We propose an alternative approach, which provides high-quality predictions of chromatin interactions using information on gene expression and CTCF-binding alone. Using multiple metrics, we confirmed that our algorithm could efficiently predict the three-dimensional architecture of both normal and rearranged genomes.
| S-EPMC6961579 | biostudies-literature
Project description:BackgroundIt is still challenging to predict interacting enhancer-promoter pairs (IEPs), partially because of our limited understanding of their characteristics. To understand IEPs better, here we studied the IEPs in nine cell lines and nine primary cell types.ResultsBy measuring the bipartite clustering coefficient of the graphs constructed from these experimentally supported IEPs, we observed that one enhancer is likely to interact with either none or all of the target genes of another enhancer. This observation implies that enhancers form clusters, and every enhancer in the same cluster synchronously interact with almost every member of a set of genes and only this set of genes. We perceived that an enhancer can be up to two megabase pairs away from other enhancers in the same cluster. We also noticed that although a fraction of these clusters of enhancers do overlap with super-enhancers, the majority of the enhancer clusters are different from the known super-enhancers.ConclusionsOur study showed a new characteristic of IEPs, which may shed new light on distal gene regulation and the identification of IEPs.
| S-EPMC7938488 | biostudies-literature
Project description:Enhancer-promoter regulation is a fundamental mechanism underlying differential transcriptional regulation. Spatial chromatin organization brings remote enhancers in contact with target promoters in cis to regulate gene expression. There is considerable evidence for promoter-enhancer interactions (PEIs). In the recent years, genome-wide analyses have identified signatures and mapped novel enhancers; however, being able to precisely identify their target gene(s) requires massive biological and bioinformatics efforts. In this review, we give a short overview of the chromatin landscape and transcriptional regulation. We discuss some key concepts and problems related to chromatin interaction detection technologies, and emerging knowledge from genome-wide chromatin interaction data sets. Then, we critically review different types of bioinformatics analysis methods and tools related to representation and visualization of PEI data, raw data processing and PEI prediction. Lastly, we provide specific examples of how PEIs have been used to elucidate a functional role of non-coding single-nucleotide polymorphisms. The topic is at the forefront of epigenetic research, and by highlighting some future bioinformatics challenges in the field, this review provides a comprehensive background for future PEI studies.
| S-EPMC5142009 | biostudies-literature
Project description:We examined how remote enhancers establish physical communication with target promoters to activate gene transcription in response to environmental signals. Although the natural IFN-beta enhancer is located immediately upstream of the core promoter, it also can function as a classical enhancer element conferring virus infection-dependent activation of heterologous promoters, even when it is placed several kilobases away from these promoters. We demonstrated that the remote IFN-beta enhancer "loops out" the intervening DNA to reach the target promoter. These chromatin loops depend on sequence-specific transcription factors bound to the enhancer and the promoter and thus can explain the specificity observed in enhancer-promoter interactions, especially in complex genetic loci. Transcription factor binding sites scattered between an enhancer and a promoter can work as decoys trapping the enhancer in nonproductive loops, thus resembling insulator elements. Finally, replacement of the transcription factor binding sites involved in DNA looping with those of a heterologous prokaryotic protein, the lambda repressor, which is capable of loop formation, rescues enhancer function from a distance by re-establishing enhancer-promoter loop formation.
| S-EPMC2779200 | biostudies-literature
Project description:A large number of distal enhancers and proximal promoters form enhancer-promoter interactions to regulate target genes in the human genome. Although recent high-throughput genome-wide mapping approaches have allowed us to more comprehensively recognize potential enhancer-promoter interactions, it is still largely unknown whether sequence-based features alone are sufficient to predict such interactions.Here, we develop a new computational method (named PEP) to predict enhancer-promoter interactions based on sequence-based features only, when the locations of putative enhancers and promoters in a particular cell type are given. The two modules in PEP (PEP-Motif and PEP-Word) use different but complementary feature extraction strategies to exploit sequence-based information. The results across six different cell types demonstrate that our method is effective in predicting enhancer-promoter interactions as compared to the state-of-the-art methods that use functional genomic signals. Our work demonstrates that sequence-based features alone can reliably predict enhancer-promoter interactions genome-wide, which could potentially facilitate the discovery of important sequence determinants for long-range gene regulation.The source code of PEP is available at: https://github.com/ma-compbio/PEP .jianma@cs.cmu.edu.Supplementary data are available at Bioinformatics online.
| S-EPMC5870728 | biostudies-literature
Project description:The classic model of eukaryotic gene expression requires direct spatial contact between a distal enhancer and a proximal promoter. Recent Chromosome Conformation Capture (3C) studies show that enhancers and promoters are embedded in a complex network of looping interactions. Here we use a polymer model of chromatin fiber to investigate whether, and to what extent, looping interactions between elements in the vicinity of an enhancer-promoter pair can influence their contact frequency. Our equilibrium polymer simulations show that a chromatin loop, formed by elements flanking either an enhancer or a promoter, suppresses enhancer-promoter interactions, working as an insulator. A loop formed by elements located in the region between an enhancer and a promoter, on the contrary, facilitates their interactions. We find that different mechanisms underlie insulation and facilitation; insulation occurs due to steric exclusion by the loop, and is a global effect, while facilitation occurs due to an effective shortening of the enhancer-promoter genomic distance, and is a local effect. Consistently, we find that these effects manifest quite differently for in silico 3C and microscopy. Our results show that looping interactions that do not directly involve an enhancer-promoter pair can nevertheless significantly modulate their interactions. This phenomenon is analogous to allosteric regulation in proteins, where a conformational change triggered by binding of a regulatory molecule to one site affects the state of another site.
| S-EPMC4207457 | biostudies-literature