{"ID": "PMID:30150754", "lab": {"title": "Keji Zhao, NHLBI", "display_title": "Keji Zhao, NHLBI", "@id": "/labs/keji-zhao-lab/", "@type": ["Lab", "Item"], "correspondence": [{"contact_email": "emhhb2tAbmhsYmkubmloLmdvdg==", "@id": "/users/44d2c6b9-15a0-4991-b84e-601e432df30f/", "display_title": "Keji Zhao"}], "status": "current", "uuid": "8017f1c9-8877-43b4-8cd5-c695621e78e5", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.8017f1c9-8877-43b4-8cd5-c695621e78e5"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/30150754", "award": {"display_title": "DEVELOPMENT OF TRAC-LOOP, A NOVEL TECHNIQUE TO DETECT GENOME-WIDE CHROMATIN INTERACTIONS", "name": "TCPA-2017-08", "status": "current", "description": "TCPA: Most current techniques for genome-wide analysis of chromatin interactions are based on the \nchromosome conformation capture (3C) technique. Because the traditional Hi-C technique uses a 6-bp restriction enzyme to cut chromatin, which usually finds one cleavage site every 5000bp in the genome, it does not have sufficient resolution for identification of enhancer-promoter interactions. Significant improvement has been achieved by the in situ Hi-C protocol, which uses a 4-bp cutter enzyme and reaches a resolution of about 1kb, thus enabling identification of specific enhancer-promoter interactions at high-resolution. However, this method requires a costly sequencing depth of 5 to 10 billions of paired-end tags (PETs) per library, which prohibits its application to a large number of samples. Other 3C-based techniques have been developed to focus on interactions at selected regions by capture Hi-C or tethered through specific proteins by ChIA-PET have helped to increase resolution by focusing on potential regulatory regions of the genome. However, a recent study compared \nchromatin interactions detected by fluorescence in situ hybridization (FISH) and 3C-based assays and found a high degree of discrepancy between the two techniques, suggesting that cross-validation of interaction data using different strategies is critical. \nWe propose to develop a novel technique, TrAC-loop, for Transposition-mediated Analysis of \nChromatin loops in the genome. The method does not require SDS-mediated partial decondensation of chromatin, restriction enzyme digestion, or proximity-based ligation of chromatin fragments. TrAC-loop directly captures interacting chromatin regions by Tn5-mediated transposition of a bivalent ME (mosaic end) linker without disrupting the nuclear structure. Thus, this novel strategy avoids potential artifacts derived from SDS-mediated partial decondensation of chromatin, restriction enzyme digestion and proximity-based re-ligation of chromatin fragments that are used in the 3C assays. Our strategy represents a shift in paradigm. All other genome-wide methods of mapping chromatin interactions use 3C-based techniques, whereas ours use transposition. Although transposition has been used to tag \nchromatin, this is the first time it is used to join chromatin segments.", "@id": "/awards/TCPA-2017-08/", "center_title": "TCPA - Zhao", "uuid": "0116e3c0-fb5a-491c-a9c2-8e17df70bfc1", "@type": ["Award", "Item"], "project": "4DN", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Trac-looping measures genome structure and chromatin accessibility.", "status": "current", "aliases": ["4dn-dcic-lab:30150754"], "authors": ["Lai B", "Tang Q", "Jin W", "Hu G", "Wangsa D", "Cui K", "Stanton BZ", "Ren G", "Ding Y", "Zhao M", "Liu S", "Song J", "Ried T", "Zhao K"], "journal": "Nature methods", "abstract": "Long-range chromatin interactions play critical roles in genome organization and  regulation of transcription. We now report transposase-mediated analysis of chromatin looping (Trac-looping) for simultaneous detection of multiscale genome-wide chromatin interactions among regulatory elements and chromatin accessibility. With this technique, a bivalent oligonucleotide linker is inserted between two interacting regions such that the chromatin interactions are captured without prior chromatin fragmentation and proximity-based ligation. Application of Trac-looping to human CD4(+) T cells revealed substantial reorganization of enhancer-promoter interactions associated with changes in gene expression after T cell receptor stimulation.", "date_created": "2019-06-10T20:09:17.261239+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2019-06-10T20:11:02.462630+00:00"}, "date_published": "2018-09", "public_release": "2019-06-10", "schema_version": "2", "project_release": "2019-06-10", "@id": "/publications/6fed1fba-d680-44db-81d3-b303f882277b/", "@type": ["Publication", "Item"], "uuid": "6fed1fba-d680-44db-81d3-b303f882277b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "Lai B et al. (2018) PMID:30150754", "external_references": [], "short_attribution": "Lai B et al. (2018)", "@context": "/terms/", "aggregated-items": {}, "validation-errors": []}