Mus musculus Raw sequence reads
RNA-chromatin interactions play a pivotal role in regulating gene expression and cellular function, yet their contributions to hematopoietic system remain poorly understood. In this study, we conducted a comprehensive analysis of RNA-chromatin interactions throughout the hematopoietic lineage and discovered that hematopoietic stem cells (HSCs) exhibit a higher density of RNA-chromatin interactions compared to committed progenitors and differentiated cells. Notably, these interactions are characterized by high levels of chromatin-associated regulatory RNAs (carRNAs) concentrated at super-enhancer domains, predominantly modified by m6A. We identified that VIRMA, an essential component of the m6A methyltransferase complex, is crucial for these interactions. The depletion of Virma disrupts RNA-chromatin interactions in HSCs, compromises their quiescence, and ultimately results in exhaustion. Mechanistically, VIRMA mediates the interaction between m6A-modified carRNAs and H3K27ac histone-modified chromatin through a mechanism dependent on liquid-liquid phase separation. Collectively, our findings highlight the role of m6A-modified carRNAs in governing chromatin architecture, thereby preserving HSC integrity.