3D Chromosomal Landscapes in Hematopoiesis and Immunity. Issue 9 (September 2019)

• Record Type: Journal Article
• Authors: Kloetgen, Andreas; Thandapani, Palaniraja; Tsirigos, Aristotelis; Aifantis, Iannis
• Is Part Of: Trends in immunology. Volume 40:Issue 9(2019)
• Page Start: 809
• Page End: 824
• Publication Date: 2019-09
• Subjects: Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2019.07.003
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : Epigenetic dysregulation plays a profound role in the pathogenesis of hematological malignancies, which is often the result of somatic mutations of chromatin regulators. Previously, these mutations were largely considered to alter gene expression in two dimensions, by activating or repressing chromatin states; however, research in the last decade has highlighted the increasing impact of the 3D organization of the genome in gene regulation and disease pathogenesis. Here, we summarize the current principles of 3D chromatin organization, how the integrity of the 3D genome governs immune cell development and malignant transformation, as well as how underlying (epi-)genetic drivers of 3D chromatin alterations might act as potential novel therapeutic targets for hematological malignancies. Highlights: The 3D chromatin architecture is emerging as an important player in the pathogenesis of hematological malignancies. Normal hematopoiesis and immune cell maturation are accompanied by widespread changes in chromatin compartments, topologically associated domains, and epigenetic features to ensure lineage commitment. Chromatin architectural changes driven by either genetic or epigenetic dysregulation can activate proto-oncogenes by altering regulatory interactions, contributing to tumorigenesis. Genetic mutations in key epigenetic players can drive cancer development by impacting 3D chromatin architecture.