Article Synopsis
- The study investigates the three-dimensional genome structure during normal B cell differentiation and in various chronic lymphocytic leukemia and mantle cell lymphoma cells by integrating multiple omics data sets.
- It identifies an intermediate compartment in genome architecture, showing dynamic changes during B cell development, where a significant portion of genomic compartments shifts from naive to activated states and back as cells mature.
- The findings reveal that B cell cancers have specific alterations in their 3D genome organization, including large chromatin structures that affect key genes related to the diseases.
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Article Abstract
To investigate the three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia and mantle cell lymphoma patients, here we integrate in situ Hi-C and nine additional omics layers. Beyond conventional active (A) and inactive (B) compartments, we uncover a highly-dynamic intermediate compartment enriched in poised and polycomb-repressed chromatin. During B cell development, 28% of the compartments change, mostly involving a widespread chromatin activation from naive to germinal center B cells and a reversal to the naive state upon further maturation into memory B cells. B cell neoplasms are characterized by both entity and subtype-specific alterations in 3D genome organization, including large chromatin blocks spanning key disease-specific genes. This study indicates that 3D genome interactions are extensively modulated during normal B cell differentiation and that the genome of B cell neoplasias acquires a tumor-specific 3D genome architecture.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844026 | PMC |
| http://dx.doi.org/10.1038/s41467-020-20849-y | DOI Listing |
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