Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA327574 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3737470.fastq.gz | Fastqsanger.gz | |||
| SRR3737480.fastq.gz | Fastqsanger.gz | |||
| SRR3737490_1.fastq.gz | Fastqsanger.gz | |||
| SRR3737490_2.fastq.gz | Fastqsanger.gz | |||
| SRR3737500_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 61 |
Similar Datasets
Project description:Genome-wide association studies (GWAS) have identified a great number of non-coding risk variants for colorectal cancer (CRC). To date, the majority of these variants have not been functionally studied. Identification of allele-specific transcription factor (TF) binding is of great importance to understand regulatory consequences of such variants. A recently developed proteome-wide analysis of disease-associated SNPs (PWAS) enables identification of DNA-TF interactions in an unbiased fashion. Here, we performed a large-scale PWAS studies to comprehensively characterize TF binding related to CRC, which identified 731 allele-specific TF binding at 116 CRC risk loci. This screen identified rs1800734 within the promoter region of MLH1 as perturbing the binding of TFAP4 and consequently increaseing DCLK3 expression through a long-range interaction, which promotes cancer progression through enhancing expression of the genes related to epithelial-to-mesenchymal transition (EMT).
2017-02-15 | GSE83968 | GEO
Project description:Genome-wide association studies have identified over 70 common variants that are associated with breast cancer risk. Most of these variants map to non-protein-coding regions; several map to gene deserts, regions of several hundred kb lacking protein-coding genes. We hypothesized that gene deserts harbour long-range regulatory elements that can physically interact with target genes to influence their expression. To test this, we developed Capture Hi-C (CHi-C), which by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. We used CHi-C to investigate long-range interactions at three breast cancer gene deserts mapping to 2q35, 8q24.21 and 9q31.2. We identified interaction peaks between putative regulatory elements ("bait fragments") within the captured regions and "targets" that included both protein-coding genes and long non-coding (lnc)RNAs, over distances of 6.6 kb to 2.6 Mb. Target protein-coding genes were IGFBP5, KLF4, NSMCE2 and MYC; target lncRNAs included DIRC3, PVT1 and CCDC26. For two gene deserts we were able to define a set of SNPs that were correlated with the published risk variant and that clustered within the bait end of an interaction peak. Preliminary functional analyses implicate one SNP (rs12613955; 2q35) as a potentially functional variant. Capture Hi-C was carried out in BT483, SUM44, and GM06990 cell lines to investigate breast cancer risk loci 2q35, 8q24.21 and 9q31.2.
2014-08-04 | E-GEOD-55634 | biostudies-arrayexpress
Project description:Genome-wide association studies have identified over 70 common variants that are associated with breast cancer risk. Most of these variants map to non-protein-coding regions; several map to gene deserts, regions of several hundred kb lacking protein-coding genes. We hypothesized that gene deserts harbour long-range regulatory elements that can physically interact with target genes to influence their expression. To test this, we developed Capture Hi-C (CHi-C), which by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. We used CHi-C to investigate long-range interactions at three breast cancer gene deserts mapping to 2q35, 8q24.21 and 9q31.2. We identified interaction peaks between putative regulatory elements ("bait fragments") within the captured regions and "targets" that included both protein-coding genes and long non-coding (lnc)RNAs, over distances of 6.6 kb to 2.6 Mb. Target protein-coding genes were IGFBP5, KLF4, NSMCE2 and MYC; target lncRNAs included DIRC3, PVT1 and CCDC26. For two gene deserts we were able to define a set of SNPs that were correlated with the published risk variant and that clustered within the bait end of an interaction peak. Preliminary functional analyses implicate one SNP (rs12613955; 2q35) as a potentially functional variant.
2014-08-04 | GSE55634 | GEO
Project description:Small RNAs target their complementary chromatin regions for gene silencing through nascent long non-coding RNAs (lncRNAs). In programmed DNA elimination of the ciliated protozoan Tetrahymena, the interaction between Piwi-associated small RNA (scnRNAs) and the lncRNA transcripts from the somatic genome has been proposed to induce target-directed scnRNA degradation (TDSD) and scnRNAs not targeted for TDSD later target the germline-limited sequences for DNA elimination. In this study, we show that the SUMO E3 ligase Ema2 is required for the accumulation of lncRNAs from somatic genome, and thus for TDSD and completing DNA elimination to make viable sexual progeny. Ema2 interacts with the SUMO E2 conjugating enzyme Ubc9 and enhances SUMOylation of the transcription regulator Spt6. We further show that Ema2 promotes the association of Spt6 and RNA polymerase II to chromatin. These results suggest that Ema2-directed SUMOylation actively promotes the lncRNA transcription that is a prerequisite for communication between the genome and small RNAs.
| MSV000092977 | MassIVE
Project description:An enhancer cluster promotes NPCs formation from ESCs through maintaining HoxB activation by long-range chromatin interaction
| PRJNA668717 | ENA
Project description:Gene transcription can be regulated by remote enhancer regions through chromosome looping either in cis or in trans. Cancer cells are characterized by wholesale changes in long-range gene interactions, but the role that these long-range interactions play in cancer progression and metastasis is not well understood. In this study, we used IGFBP3, a gene involved in breast cancer pathogenesis, as bait in a 4C-seq experiment comparing normal breast cells (HMEC) with two breast cancer cell lines (MCF7, an ER positive cell line, and MDA-MB-231, a triple negative cell line). The IGFBP3 long-range interaction profile was substantially altered in breast cancer. Many interactions seen in normal breast cells are lost and novel interactions appear in cancer lines. We found that in HMEC, the breast carcinoma amplified sequence gene family (BCAS) 1-4 were among the top 10 most significantly enriched regions of interaction with IGFBP3. 3D-FISH analysis indicated that the translocation-prone BCAS genes, which are located on chromosomes 1, 17 and 20, are in close physical proximity with IGFBP3 and each other in normal breast cells. We also found that epidermal growth factor receptor (EGFR), a gene implicated in tumorigenesis, interacts significantly with IGFBP3 and that this interaction may play a role in their regulation. Breakpoint analysis suggests that the interchromosomal rearrangements seen in the MCF7 cancer cell line involve regions that engage in long-range interactions in normal breast cells. Overall, our data from multiple lines of evidence suggest an important role for long-range chromosomal interactions in the pathogenesis of cancer. Comparison of IGFBP3 interaction profiles in normal breast tissue and 2 breast tumor subtypes
2013-08-03 | E-GEOD-49521 | biostudies-arrayexpress
Project description:Non-coding variants coordinate transcription factor (TF) binding and chromatin mark enrichment changes over regions spanning >100 kb. We named these molecularly coordinated regions “variable chromatin modules” (VCMs), providing a conceptual framework of how regulatory variation might shape complex traits. To better understand the molecular mechanisms underlying VCM formation, here, we mechanistically dissect an uncharacterized VCM-modulating non-coding variant that is associated with reduced chronic lymphocytic leukemia (CLL) predisposition and disease progression. This common, germline variant constitutes a 5-bp indel that controls the activity of an AXIN2 gene-linked VCM by creating a MEF2 binding site, which, upon binding, activates a super-enhancer-like regulatory element. This triggers a big change in TF binding activity and chromatin state at an enhancer cluster spanning >150 kb, coinciding with long-range chromatin compaction and AXIN2 up-regulation. Our results support a model in which the indel acts as an AXIN2 VCM-activating TF nucleation event, which modulates CLL pathology.
2022-04-21 | PXD029313 | Pride
Project description:Naturally occurring mutations in the γ-globin promoters can result in hereditary persistence of fetal hemoglobin (HPFH), a benign condition that ameliorates the severity of β-hemoglobinopathies through increased post-natal fetal hemoglobin (HbF) expression. Base editing to recreate the HPFH mutations is a promising approach to induce HbF. Compared with Cas9-generated indels, base-editing approaches were more potent, with the −175 A>G conversion resulting in the strongest induction of HbF by creating a new TAL1 binding motif that stimulates long-range interaction with the locus control region (LCR), a powerful upstream enhancer. Micro-Capture-C analysis showed that introducing the −175 A>G variant stimulated long-range interaction between the γ-globin promoters and the LCR in erythroid progenitor cell line. Together, these findings show that the −175 A>G variant creates a bipartite GATA–TAL1 motif, resulting in the assembly of a GATA1/TAL1/LMO2/LDB1 complex, which activates γ-globin gene transcription by enhancing its physical association with the LCR.
2023-04-28 | GSE228570 | GEO
Project description:we find METTL3 associates with polyribosomes and promotes translation. METTL3 depletion inhibits translation, and both wild-type and catalytically inactive METTL3 promote translation when tethered to the 3' untranslated region (UTR) of a reporter mRNA. Mechanistically, METTL3 enhances mRNA translation through an interaction with the translation initiation machinery. m6A seq in A549 and H1299 cells, RNA seq in METTL3 knockdown cells
2016-07-03 | E-GEOD-76367 | biostudies-arrayexpress