Alternative DNA structures in hematopoiesis and adaptive immunity

Besides the canonical B-form, DNA also adopts alternative non-B form conformations which are highly conserved in all domains of life. While extensive research over decades has centered on the genomic functions of B-form DNA, understanding how non-B-form conformations influence functional genomic states remains a fundamental and open question. Recent studies have ascribed alternative DNA conformations such as G-quadruplexes and R-loops as important functional features in eukaryotic genomes. This review delves into the biological importance of alternative DNA structures, with a specific focus on hematopoiesis and adaptive immunity. We discuss the emerging roles of G-quadruplex and R-loop structures, the two most well-studied alternative DNA conformations, in the hematopoietic compartment and present evidence for their functional roles in normal cellular physiology and associated pathologies.