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Given that chromosome and nuclear organization is tightly linked to biological state of the cell, the center will map the 4D nucleome for four key biological states representing different conformations during the cell cycle (interphase and mitosis), and during cell differentiation (pluripotent and differentiated states). We will obtain complementary data regarding the structure and dynamics of chromatin, at different length scales and in single cells using extensive high-throughput imaging, live cell imaging and super resolution microscopy. Data obtained with all approaches will be analyzed, integrated and modeled using a set of methods we will further develop to gain insights into the structure, physics and dynamics of chromosome folding over different length scales. Finally, a critical component of our proposal is the biological validation and further elaboration of the chromatin interaction maps that are generated from our conformational analyses. This validation will be achieved through site-specific editing of genomic sequence and epigenetic marks, the creation of new contact points within the genome, and the identification of factors (both protein and nucleic acid) that facilitat or restrict these interactions. Effects of such perturbations in the chromosome conformation on transcription will reveal relationships between specific chromosome structural features and gene expression.", "center_title": "NOFIC - Dekker", "@id": "/awards/1U54DK107980-01/", "status": "current", "project": "4DN", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "files": [{"file_classification": "raw file", "notes_to_tsv": ["The experiment linked to this file was initially submitted as \"Dilution Hi-C\" but it was subsequently determined that the correct experiment type is \"in situ Hi-C\". 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