“…1a), and cellular formation of G4s has been demonstrated to play key roles in transcription, genomic and epigenetic instability, aging processes, and cancer development 2 . As the diverse functions of G4s are often governed by their interaction with G4-binding proteins, studies in recent years have been focused on identifying G4-binding proteins 2,3 ; however, their biochemical and mechanistic roles are still not well characterized. In this issue, Li et al 4 identified Yin Yang 1 (YY1) as a novel G4-binding protein that directly interacts with the G4 structure and revealed that such YY1-G4 interaction contributed to long-range DNA looping and regulated the expression of proximal and distal genes (Fig.…”