Genomic profiling of PML bodies by ALaP-seq reveals transcriptional regulation by PML bodies through the DNMT3A exclusion
Description
The promyelocytic leukemia (PML) body is a phase-separated nuclear structure physically associated with chromatin, implying its crucial roles in genome functions. However, its role in transcriptional regulation is largely unknown. We developed APEX-mediated chromatin labeling and purification (ALaP) to identify the genomic regions proximal to PML bodies. We found that PML bodies associate with active regulatory regions across the genome and with an ~300 kb of the short arm of the Y chromosome (YS300) in mouse embryonic stem cells. The PML body-association with YS300 is essential for the transcriptional activity of the neighboring Y-linked clustered genes. Mechanistically, PML bodies provide specific nuclear spaces that the de novo DNA methyltransferase DNMT3A cannot access, resulting in the steady maintenance of a hypomethylated state at Y-linked gene promoters. Our study underscores a new mechanism for gene regulation in the 3D-nuclear space and provides insights into the functional properties of nuclear structures for genome function.