Abstract
Proper lymphopoiesis and immune responses depend on the spatiotemporal control of multiple processes, including gene expression, DNA recombination and cell fate decisions. High-order 3D chromatin organization is increasingly appreciated as an important regulator of these processes and dysregulation of genomic architecture has been linked to various immune disorders, including lymphoid malignancies. In this review, we present the general principles of the 3D chromatin topology and its dynamic reorganization during various steps of B and T lymphocyte development and activation. We also discuss functional interconnections between architectural, epigenetic and transcriptional changes and introduce major key players of genomic organization in B/T lymphocytes. Finally, we present how alterations in architectural factors and/or 3D genome organization are linked to dysregulation of the lymphopoietic transcriptional program and ultimately to hematological malignancies.
Highlights
Over the past decades, plethora of studies have documented the transcriptional network that controls immune cell regulation and plasticity during lymphocyte development and differentiation [1,2,3]
T cell receptors (TCR) activation led to formation of de novo short-range chromatin loops, resulting in increased intra-topologically associating domains (TADs) connectivity in more than 60% of TADs in both CD4+ and CD8+ cells
This study demonstrated a correlation between increased intra-TAD activity and transcriptional upregulation as well as higher boundary insulation enriched with CTCF and Notch binding
Summary
Plethora of studies have documented the transcriptional network that controls immune cell regulation and plasticity during lymphocyte development and differentiation [1,2,3]. At the finest scale of organization, chromatin is organized into looped structures or chromatin contacts that enable physical proximity among distal regulatory elements (RE), such as enhancers and promoters These long-range interactions have been shown to play important roles in key biological processes, including DNA recombination and regulation of gene expression and cell fate [33,34,35,36]. A large number of studies started mapping the hierarchical levels of 3D chromatin architecture in various stages of lymphopoiesis and immune response and reveal important insights for its role in VDJ recombination, gene expression and cell fate decisions.
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