H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE133183 | GEO | 2020/12/01
REPOSITORIES: GEO
Similar Datasets
Project description:H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions
| PRJNA550207 | ENA
Project description:<p>We characterized the epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes (FLS) compared with osteoarthritis FLS. Multiple technologies were used, including ChIP-seq to assay H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3, ATAC-seq for chromatin accessibility, the transcriptome by RNA-seq and whole genomic bisulfite sequencing for DNA methylation. Integrative analysis was performed using a novel unbiased method to identify regions of the genome that have similar epigenetic marks. The regions that distinguished RA and osteoarthritis cells were primarily located in active enhancers and promoters. The regions and genes identified included immunological pathways. In addition, some unexpected pathways, most notably "Huntington's Disease Signaling", were discovered. The Huntington's Disease pathway was biologically validated for Huntingtin-interacting protein-1, which regulated invasive behavior of FLS. For a complete description, see R. Ai <i>et al.</i>, Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes. <i>Nat Commun</i> 9, 1921 (2018).</p> <p>Sequencing data of study participants are available through dbGaP's Authorized Access portal, while analyses of the sequencing data may be obtained through NCBI's GEO portal under <a href="https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112658">GSE112658.</a></p>
| phs001615 | dbGaP
Project description:In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increase of histone H3 lysine 27 acetylation (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is affected by these events is unclear. Here, by comparing chromatin structure and H3K27ac levels in normal and lymphoma B-cells, we show that enhancer-promoter interacting regions assume different conformations according to the local abundance of H3K27ac. Genetic or pharmacologic depletion of H3K27ac decreases the frequency and the spreading of these interactions, altering oncogene expression. Moreover, enhancer hijacking mediated by chromosomal translocations influences the epigenetic status of the regions flanking the breakpoint, prompting the formation of distinct intra-chromosomal interactions in the two homologous chromosomes. These interactions are accompanied by allele-specific gene expression changes. Overall, our work indicates that H3K27ac dynamics modulate interaction frequency between regulatory regions and can lead to allele-specific chromatin configurations to sustain oncogene expression.
2021-03-09 | GSE168472 | GEO
Project description:In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increase of histone H3 lysine 27 acetylation (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is affected by these events is unclear. Here, by comparing chromatin structure and H3K27ac levels in normal and lymphoma B-cells, we show that enhancer-promoter interacting regions assume different conformations according to the local abundance of H3K27ac. Genetic or pharmacologic depletion of H3K27ac decreases the frequency and the spreading of these interactions, altering oncogene expression. Moreover, enhancer hijacking mediated by chromosomal translocations influences the epigenetic status of the regions flanking the breakpoint, prompting the formation of distinct intra-chromosomal interactions in the two homologous chromosomes. These interactions are accompanied by allele-specific gene expression changes. Overall, our work indicates that H3K27ac dynamics modulate interaction frequency between regulatory regions and can lead to allele-specific chromatin configurations to sustain oncogene expression.
2021-03-09 | GSE168471 | GEO
Project description:In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increase of histone H3 lysine 27 acetylation (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is affected by these events is unclear. Here, by comparing chromatin structure and H3K27ac levels in normal and lymphoma B-cells, we show that enhancer-promoter interacting regions assume different conformations according to the local abundance of H3K27ac. Genetic or pharmacologic depletion of H3K27ac decreases the frequency and the spreading of these interactions, altering oncogene expression. Moreover, enhancer hijacking mediated by chromosomal translocations influences the epigenetic status of the regions flanking the breakpoint, prompting the formation of distinct intra-chromosomal interactions in the two homologous chromosomes. These interactions are accompanied by allele-specific gene expression changes. Overall, our work indicates that H3K27ac dynamics modulate interaction frequency between regulatory regions and can lead to allele-specific chromatin configurations to sustain oncogene expression.
2021-03-09 | GSE168470 | GEO
Project description:Silencers active in the Drosophila embryonic mesoderm were identified by reporter assays in dissociated embryonic cells. We find that, despite the presence of ChIP peaks for known transcriptional corepressors and marks of repressed chromatin, the only significantly enriched source of mesodermal silencers is non-mesodermal enhancers. We present evidence that a subset of silencers acts by looping to target promoters.
2019-09-25 | GSE137949 | GEO
Project description:The most prominent model for long-range enhancer regulation involves direct enhancer-promoter interaction by looping out the intervening chromatin. Using a synthetic biology approach, we have determined that a chromatin unfolding between Shh and its enhancers is regulated specifically by the Shh-Brain-Enhancers and is mediated by the recruitment of Poly (ADP-Ribose) Polymerase 1. This ‘chromatin unfolding’ model represents a new mechanism of long-range enhancer-promoter communication in addition to the looping and tracking models. ChIP-on-chip for H3K27me3 and H3K27ac on the Shh regulatory region on ESCs and transfected ESCs showed a gain of H3k27ac specifically on active enhancers and no loss of Polycomb marks upon Shh activation.
2018-12-01 | GSE115642 | GEO
Project description:Cohesin is implicated in establishing tissue-specific DNA loops that target enhancers to promoters, and also localizes to sites bound by the insulator protein CTCF, which blocks enhancer-promoter communication. However, cohesin-associated interactions have not been characterized on a genome-wide scale. Here we performed chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) of the cohesin subunit SMC1A in developing mouse limb. We identified 2,264 SMC1A interactions, of which 1,491 (65%) involved sites co-occupied by CTCF. SMC1A participates in tissue- specific enhancer-promoter interactions and interactions that demarcate regions of correlated regulatory output. In contrast to previous studies, we also identified interactions between promoters and distal sites that are maintained in multiple tissues, but are poised in embryonic stem cells and resolve to tissue-specific activated or repressed chromatin states in the mouse embryo. Our results reveal the diversity of cohesin- associated interactions in the genome and highlight their role in establishing the regulatory architecture of development. Smc1a ChIA-PET, RNA-seq, chromatin state maps (H3K27ac, H3K27me3, H3K4m2), and CTCF and Smc1a binding in mouse embryonic limb bud (E11.5)
2013-05-22 | E-GEOD-42237 | biostudies-arrayexpress
Project description:Copy number variants (CNV) influence the expression of genes that map not only within, but also on their flanks. To assess the possible mechanism(s) underlying this “neighboring effect”, we compared intrachromosomal interactions and histone modifications in cell lines of patients affected by genomic disorders and control individuals. We detected alteration of intrachromosomal interactions (chromosomal looping) between the loci of affected genes and the rearranged interval using chromosome conformation capture (4C-seq). These results are consistent with the observed gene expression alterations. We also pinpointed concomitant changes in histone modifications between samples. Modified genes were often looping together, possibly forming an interacting cluster. We conclude that large genomic rearrangements can lead to chromatin conformation changes that extend far away from the structural variant, thus possibly modulating expression globally and modifying the phenotype. For example, we observe that the chromatin conformation, histone marks and relative expression levels of the AUTS2 gene, mutations of which are associated with autism and intellectual disabilities, are modified in Williams-Beuren syndrome patients cell lines. Examination of 2 different histone modifications in genomic disorders patients' cell lines.
2013-11-16 | E-GEOD-33784 | biostudies-arrayexpress
Project description:Amartya Sanyal mailto:amartya.sanyal@umassmed.edu (Wet Lab), Bryan R. Lajoie mailto:bryan.lajoie@umassmed.edu, Gaurav Jain mailto:gaurav.jain@umassmed.edu (Dry Lab), Job Dekker mailto:job.dekker@umassmed.edu (Principal Investigator) This track contains chromatin interaction data generated using the 5C (Chromatin Conformation Capture Carbon Copy) method by the ENCODE group (Dekker Lab) located at the University of Massachusetts, Worcester, MA. This track shows the significant looping interactions between transcriptional start sites (TSS) and distal regulatory elements in the context of the 44 ENCODE pilot regions spanning 1% of the human genome. Although the DNA is a linear sequence, the chromatin, which is packed and organized inside the nucleus, does not function linearly. This is most clearly illustrated by the fact that genes are often regulated by elements that are located hundreds of kilobases away in the linear genome. Imaging techniques have shown that regulatory elements can act over large genomic distances by engaging in direct physical interactions with target genes, resulting in the formation of chromatin loops. Based on these observations, we have envisaged that the spatial organization of the genome resembles a three-dimensional network that is driven by physical associations between genes and regulatory elements, both in cis (within the same chromosome) and in trans (between different chromosomes) (Dekker, 2006). Apart from imaging technology which is labor intensive and low-throughput, long-range chromatin looping interactions can be detected using the Chromosome Conformation Capture (3C) technology (Dekker et al., 2002). The 3C method employs formaldehyde cross-linking to covalently link interacting chromatin segments in intact cells. Cells are subsequently lysed and chromatin is digested with a restriction enzyme of choice. The digested fragments are then ligated under dilute conditions to facilitate intramolecular ligation. The result is a genome-wide interaction library of ligation products corresponding to all possible chromatin interactions. Specific ligation products can then be detected by PCR using specific primer pairs. The 5C method was developed to dramatically increase 3C throughput (Dostie et al., 2006; Dostie and Dekker, 2007). The 5C method greatly increases the scale of chromatin interaction detection by replacing the PCR detection step of 3C with ligation-mediated amplification (LMA). LMA is advantageous due to a much higher level of multiplexing by using thousands of primers in a single reaction to detect millions of chromatin interactions (ligation junctions) in parallel. The LMA step effectively "copies" 3C ligation products into much smaller 5C ligation products that precisely correspond to ligation junctions formed during the 3C procedure. The products of the multiplexed LMA reaction constitute the 5C library. The composition of the 5C library is determined using high-throughput DNA sequencing. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf The aim of the pilot study was to generate a "connectivity map" between transcription start sites (TSS) and distal regulatory elements within the 44 ENCODE PILOT regions. In the current scheme, 5C primers were designed for all HindIII restriction fragments. Reverse primers were designed on fragments containing the TSS of annotated genes. Forward primers were designed on all other fragments. This design allowed for the interrogation of all TSS with all other restriction fragments, thus generating an interaction map between TSS and regulatory elements. For gene desert ENCODE pilot regions (for example ENr313), an altered scheme of forward and reverse primers was designed. Primers were selected for relative uniqueness using a custom 15-mer frequency table and BLAST. A custom hexamer barcode was added to each primer to ensure the sequence was unique relative to the primer pool being used. Primers were also selected for the appropriate melting temperature and GC-content and a universal tail sequence for amplification. The 44 ENCODE regions were analyzed in two groups using two separate 5C primer pools. The first group (ENm) contained the manually-picked ENCODE regions, ENm001-014 and ENr313. The second group (ENr) contained the 30 randomly-picked ENCODE regions. The two 5C primer pools were made by pooling 5C primers for interrogating long-range interactions in the two groups of ENCODE regions. The primer pool for the ENm group contained a total of 3,150 primers (476 reverse 5C primers and 2674 forward 5C primers). This primer pool allowed interrogation of a total of 1,272,824 interactions. Of these, 83,427 interactions were between fragments that were both located in the same ENCODE region. This primer pool for the ENr group contained a total of 3,152 primers (505 reverse 5C primers and 2647 forward 5C primers). This primer pool allowed interrogation of a total of 1,336,735 interactions. Of these, 34,859 interactions were between fragments that were both located in the same ENCODE region. In total, 981 reverse primers and 5,321 forward primers were designed (corresponding to ~77.1% (6,302/8,174) of all HindIII fragments in the 44 ENCODE regions). Currently, data for two biological replicates have been generated for ENCODE Tier I (GM12878 and K562), Tier II (HeLa-S3), and H1 human embryonic stem cells (H1-hESC), spanning 14 ENCODE manual regions along with one random region (ENr313) as well as 30 random regions separately using high-throughput paired-end sequencing in the Illumina GA2 platform. The looping interactions, which are detected in both the biological replicates, are considered significant.
2012-07-18 | E-GEOD-39510 | biostudies-arrayexpress