{"lab": {"@id": "/labs/siyuan-wang-lab/", "uuid": "7f49b420-d2ae-4de4-820a-21403dc0749f", "correspondence": [{"contact_email": "c2l5dWFuLndhbmdAeWFsZS5lZHU=", "@id": "/users/774c29b8-db1e-48bc-9669-a3e380f435c2/", "display_title": "Siyuan Wang"}], "display_title": "Siyuan Wang, YALE", "status": "current", "@type": ["Lab", "Item"], "title": "Siyuan Wang, YALE", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.7f49b420-d2ae-4de4-820a-21403dc0749f"]}}, "award": {"center_title": "OFHHD - Schatz", "project": "4DN", "name": "1U01CA260701-01", "@type": ["Award", "Item"], "uuid": "f959fce7-bd94-4a8d-961d-8c72a4eaa1ad", "@id": "/awards/1U01CA260701-01/", "description": "OFHHD: During the humoral immune response, somatic hypermutation (SHM) introduces point mutations in rearranged immunoglobulin (Ig) genes of activated germinal center (GC) B cells. SHM is essential for the fine-tuning of antibody affinity, the generation of B cells expressing high-affinity antibody, and the efficacy of many vaccines. Mistargeted SHM activities can lead to mutations and chromosomal translocations that contribute to the development of B cell lymphoma. Recent studies suggest that the three-dimensional (3D) organization of the genome regulates SHM targeting and mistargeting. However, it is largely unknown how the genome is spatially organized across multiple length scales in GC B cell development and lymphoma, and how 3D genome architecture mechanistically affects the targeting and mistargeting of SHM. Conventional approaches cannot address these questions in the primary GC tissue environment due to technical limitations. Here, we propose to apply a new method recently developed by our team, termed Multiplexed Imaging of Nucleome Architectures (MINA), to primary human tonsil tissue samples and malignant GC-derived human B cell lymphomas. We will investigate and test the association between SHM susceptibility and a variety of 3D nucleome architectures, including topologically associating domain (TAD) architecture, phase separation, and nuclear positioning of genomic regions relative to nuclear lamina, nucleoli, and nuclear pores. Through targeted genomic perturbations in human B cell lymphomas, we will test specific hypotheses linking SHM targeting elements to elevated chromatin looping interactions, TAD phase separation, nuclear pore proximity, and mutation vulnerability. Our study will significantly advance our understanding of the role of 3D genome architecture and nuclear organization in GC B cells undergoing SHM in both the developmental and tumorigenesis contexts. 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Active and inactive X chromosomes adopt different folding  and compartmentalization configurations. These results suggest that the spatial  organization of chromatin domains can change in response to regulation.", "authors": ["Wang S", "Su JH", "Beliveau BJ", "Bintu B", "Moffitt JR", "Wu CT", "Zhuang X"], "status": "current", "@type": ["Publication", "Item"], "uuid": "6162d287-5782-4f40-aacd-d5da75f0770e", "journal": "Science (New York, N.Y.)", "title": "Spatial organization of chromatin domains and compartments in single chromosomes.", "date_published": "2016-08-05", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"@id": "/publications/6162d287-5782-4f40-aacd-d5da75f0770e/", "short_attribution": "Wang S et al. (2016)", "uuid": "6162d287-5782-4f40-aacd-d5da75f0770e", "ID": "PMID:27445307", "abstract": "The spatial organization of chromatin critically affects genome function. Recent  chromosome-conformation-capture studies have revealed topologically associating  domains (TADs) as a conserved feature of chromatin organization, but how TADs are  spatially organized in individual chromosomes remains unknown. Here, we developed  an imaging method for mapping the spatial positions of numerous genomic regions  along individual chromosomes and traced the positions of TADs in human interphase  autosomes and X chromosomes. We observed that chromosome folding deviates from  the ideal fractal-globule model at large length scales and that TADs are largely  organized into two compartments spatially arranged in a polarized manner in  individual chromosomes. Active and inactive X chromosomes adopt different folding  and compartmentalization configurations. 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