Dynamics of genome architecture and chromatin function during human B cell differentiation and neoplastic transformation

Nat Commun. 2021 Jan 28;12(1):651. doi: 10.1038/s41467-020-20849-y.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / genetics*
  • Cell Transformation, Neoplastic / genetics*
  • Chromatin / genetics*
  • Chromatin Assembly and Disassembly / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genome, Human / genetics*
  • Genomics / methods
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Lymphoma, Mantle-Cell / genetics
  • Lymphoma, Mantle-Cell / pathology


  • Chromatin