scholarly journals DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis

2019 ◽  
Author(s):  
Ping Hong ◽  
Hao Jiang ◽  
Weize Xu ◽  
Da Lin ◽  
Qian Xu ◽  
...  
Keyword(s):  
Target Genes ◽  
High Efficiency ◽  
New Technology ◽  
Large Data ◽  
Regulatory Elements ◽  
Chromosome Conformation Capture ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
Effective Cost

AbstractBackgroundIt is becoming increasingly important to understand the mechanism of regulatory elements on target genes in long-range genomic distance. 3C (Chromosome Conformation Capture) and its derived methods are now widely applied to investigate genome organizations and gene regulation. Digestion-Ligation-Only Hi-C (DLO Hi-C) is a new technology with high efficiency and effective cost for whole-genome chromosome conformation capture.ResultsHere, we introduce DLO Hi-C Tool, a flexible and versatile pipeline for processing DLO Hi-C data from raw sequencing reads to normalized contact maps and providing quality controls for different steps. It includes more efficient iterative mapping and linker filtering. We applied DLO Hi-C Tool to different DLO Hi-C datasets, and demonstrated its ability of processing large data in multi-threading.ConclusionsDLO Hi-C Tool is suitable for processing DLO Hi-C and in situ DLO Hi-C datasets. It is convenient and efficient for DLO Hi-C data processing.

scholarly journals The DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 289 ◽  
Author(s):  
Ping Hong ◽  
Hao Jiang ◽  
Weize Xu ◽  
Da Lin ◽  
Qian Xu ◽  
...  
Keyword(s):  
Target Genes ◽  
High Efficiency ◽  
New Technology ◽  
Three Dimensional ◽  
Large Data ◽  
Regulatory Elements ◽  
Chromosome Conformation Capture ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
3D Genome

It is becoming increasingly important to understand the mechanism of regulatory elements on target genes in long-range genomic distance. 3C (chromosome conformation capture) and its derived methods are now widely applied to investigate three-dimensional (3D) genome organizations and gene regulation. Digestion-ligation-only Hi-C (DLO Hi-C) is a new technology with high efficiency and cost-effectiveness for whole-genome chromosome conformation capture. Here, we introduce the DLO Hi-C tool, a flexible and versatile pipeline for processing DLO Hi-C data from raw sequencing reads to normalized contact maps and for providing quality controls for different steps. It includes more efficient iterative mapping and linker filtering. We applied the DLO Hi-C tool to different DLO Hi-C datasets and demonstrated its ability in processing large data with multithreading. The DLO Hi-C tool is suitable for processing DLO Hi-C and in situ DLO Hi-C datasets. It is convenient and efficient for DLO Hi-C data processing.

scholarly journals KAP1-associated transcriptional inhibitory complex regulates C2C12 myoblasts differentiation and mitochondrial biogenesis via miR-133a repression

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Jialing Zhang ◽  
Chaoju Hua ◽  
Yu Zhang ◽  
Peng Wei ◽  
Yaping Tu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Affinity Purification ◽  
Regulatory Elements ◽  
C2c12 Myoblasts ◽  
Regulatory Machinery ◽  
New Ideas ◽  
Biogenesis Of Mitochondria

Abstract The differentiation of myoblasts plays a key role in the growth of biological individuals and the reconstruction of muscle tissue. Several microRNAs are significantly upregulated during the differentiation of myoblasts and their target genes have been explored. However, the molecular mechanisms underlying the transcriptional regulation of microRNAs remain elusive. In the present study, we found that the expression of miR-133a is increased during the differentiation of C2C12 myoblasts. miR-133a mimic is sufficient to induce the biogenesis of mitochondria and differentiation of C2C12 myoblasts whereas miR-133a inhibitor abolishes cell differentiation. Using CRISPR affinity purification in situ of regulatory elements (CAPTURE) technique, we further dissected the regulatory mechanisms of miR-133a expression and found that KAP1-associated transcription complex accounts for the suppression of miR-133a in C2C12 myoblasts. Knockdown of KAP1 increased the expression of miR-133a, which contributed to the biogenesis of mitochondria and differentiation of C2C12 myoblasts. To our knowledge, this is the first study using the CAPTURE technology to identify the regulatory factors of miR-133a during cell differentiation, which may provide new ideas for understanding the precision regulatory machinery of microRNAs during different biological processes.

scholarly journals EPEN-04. ONCOGENIC 3D TUMOR GENOME ORGANIZATION IDENTIFIES NEW THERAPEUTIC TARGETS IN EPENDYMOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii308-iii308
Author(s):  
Konstantin Okonechnikov ◽  
Jens-Martin Hübner ◽  
Owen Chapman ◽  
Abhijit Chakraborty ◽  
Meghana Pagadala ◽  
...  
Keyword(s):  
Copy Number ◽  
Target Genes ◽  
Chromosomal Rearrangements ◽  
Regulatory Elements ◽  
Chromosome 1 ◽  
Poor Survival ◽  
Chromosome Conformation ◽  
Ongoing Work ◽  
Gene Enhancer ◽  
Complex Structural

Abstract By profiling enhancers in primary ependymoma tumors, we have recently identified putative oncogenes, molecular targets, and functional pathways. Inhibition of selected targets diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymoma. While enhancers frequently regulate the nearest gene, identification of enhancer target genes remains to be a challenge in the absence of chromosome conformation information. Consequently, we have now used HiC to map the 3-dimensional organization of tumor chromatin in the two most common and aggressive ependymoma subgroups: posterior fossa group A (PF-EPN-A) and supratentorial ependymomas with gene fusions involving the NF-κB subunit gene RELA (ST-EPN-RELA). By an integrative analysis of enhancer and gene expression in the context of the newly derived HiC data, we find that a large number of the predicted enhancer target genes are enriched for strong physical interactions. Importantly, we also identify many new putative tumor-dependency genes activated by long-range promoter-enhancer interactions and complex tumor-specific chromatin clusters of regulatory elements. Complementary to the analysis of gene-enhancer interactions, we have also leveraged the HiC data for resolving structural rearrangements underlying copy number alterations. Copy number gains of the 1q arm of chromosome 1 are especially associated with poor survival. Our preliminary results in PFA relapse samples show complex structural variants underlying 1q gain that lead to inter-chromosomal rearrangements and affect several genes that potentially contribute to poor survival. In ongoing work we are testing the relevance of the novel candidate genes for tumor cell growth and proliferation in-patient derived ependymoma models.

scholarly journals Characteristic arrangement of nucleosomes is predictive of chromatin interactions at kilobase resolution

2016 ◽  
Author(s):  
Hui Zhang ◽  
Feifei Li ◽  
Yan Jia ◽  
Bingxiang Xu ◽  
Yiqun Zhang ◽  
...  
Keyword(s):  
Interaction Analysis ◽  
Low Cost ◽  
Genome Structure ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromosome Conformation Capture ◽  
Computational Method ◽  
Chromatin Interaction ◽  
Chromosome Conformation ◽  
Interaction Sites

AbstractHigh-throughput chromosome conformation capture technologies, such as Hi-C, have made it possible to survey 3D genome structure. However, the ability to obtain 3D profiles at kilobase resolution at low cost remains a major challenge. Therefore, we herein report a computational method to precisely identify chromatin interaction sites at kilobase resolution from MNase-seq data, termed chromatin interaction site detector (CISD), and a CISD-based chromatin loop predictor (CISD_loop) that predicts chromatin-chromatin interaction (CCI) from low-resolution Hi-C data. The methods are built on a hypothesis that CCIs result in a characteristic nucleosome arrangement pattern flanking the interaction sites. Accordingly, we show that the predictions of CISD and CISD_loop overlap closely with chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) anchors and loops, respectively. Moreover, the methods trained in one cell type can be applied to other cell types with high accuracy. The validity of the methods was further supported by chromosome conformation capture (3C) experiments at 5kb resolution. Finally, we demonstrate that only modest amounts of MNase-seq and Hi-C data are sufficient to achieve ultrahigh resolution CCI map. The predictive power of CISD/CISD_loop supports the hypothesis that CCIs induce local nucleosome rearrangement and that the pattern may serve as probes for 3D dynamics of the genome. Thus, our method will facilitate precise and systematic investigations of the interactions between distal regulatory elements on a larger scale than hitherto have been possible.

scholarly journals ENdb: a manually curated database of experimentally supported enhancers for human and mouse

2019 ◽  
Author(s):  
Xuefeng Bai ◽  
Shanshan Shi ◽  
Bo Ai ◽  
Yong Jiang ◽  
Yuejuan Liu ◽  
...  
Keyword(s):  
Target Genes ◽  
Regulatory Elements ◽  
Luciferase Reporter ◽  
Chromosome Conformation ◽  
Related Information ◽  
Intergenic Regions ◽  
On Chip ◽  
User Friendly ◽  
Human And Mouse

Abstract Enhancers are a class of cis-regulatory elements that can increase gene transcription by forming loops in intergenic regions, introns and exons. Enhancers, as well as their associated target genes, and transcription factors (TFs) that bind to them, are highly associated with human disease and biological processes. Although some enhancer databases have been published, most only focus on enhancers identified by high-throughput experimental techniques. Therefore, it is highly desirable to construct a comprehensive resource of manually curated enhancers and their related information based on low-throughput experimental evidences. Here, we established a comprehensive manually-curated enhancer database for human and mouse, which provides a resource for experimentally supported enhancers, and to annotate the detailed information of enhancers. The current release of ENdb documents 737 experimentally validated enhancers and their related information, including 384 target genes, 263 TFs, 110 diseases and 153 functions in human and mouse. Moreover, the enhancer-related information was supported by experimental evidences, such as RNAi, in vitro knockdown, western blotting, qRT-PCR, luciferase reporter assay, chromatin conformation capture (3C) and chromosome conformation capture-on-chip (4C) assays. ENdb provides a user-friendly interface to query, browse and visualize the detailed information of enhancers. The database is available at http://www.licpathway.net/ENdb.

scholarly journals Chromosome looping at the human α-globin locus is mediated via the major upstream regulatory element (HS −40)

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4253-4260 ◽  
Author(s):  
Douglas Vernimmen ◽  
Fatima Marques-Kranc ◽  
Jacqueline A. Sharpe ◽  
Jacqueline A. Sloane-Stanley ◽  
William G. Wood ◽  
...  
Keyword(s):  
Long Range ◽  
Regulatory Element ◽  
Globin Gene ◽  
Regulatory Elements ◽  
Chromosome Conformation ◽  
Long Range Interactions ◽  
Upstream Regulatory Element ◽  
Physical Interactions ◽  
Globin Promoter

Abstract Previous studies in the mouse have shown that high levels of α-globin gene expression in late erythropoiesis depend on long-range, physical interactions between remote upstream regulatory elements and the globin promoters. Using quantitative chromosome conformation capture (q3C), we have now analyzed all interactions between 4 such elements lying 10 to 50 kb upstream of the human α cluster and their interactions with the α-globin promoter. All of these elements interact with the α-globin gene in an erythroid-specific manner. These results were confirmed in a mouse model of human α globin expression in which the human cluster replaces the mouse cluster in situ (humanized mouse). We have also shown that expression and all of the long-range interactions depend largely on just one of these elements; removal of the previously characterized major regulatory element (called HS −40) results in loss of all the interactions and α-globin expression. Reinsertion of this element at an ectopic location restores both expression and the intralocus interactions. In contrast to other more complex systems involving multiple upstream elements and promoters, analysis of the human α-globin cluster during erythropoiesis provides a simple and tractable model to understand the mechanisms underlying long-range gene regulation.

scholarly journals Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization

2014 ◽  
Vol 28 (24) ◽  
pp. 2778-2791 ◽  
Author(s):  
Iain Williamson ◽  
Soizik Berlivet ◽  
Ragnhild Eskeland ◽  
Shelagh Boyle ◽  
Robert S. Illingworth ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Genome Organization ◽  
Chromosome Conformation Capture ◽  
Chromosome Conformation ◽  
Spatial Genome Organization
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