Phasing single-molecule nano-NOMe-seq reveals chromatin state heterogeneity in the context of transcription and long-range interactions.

ABSTRACT: A central challenge in molecular biology is determining how 3D chromatin architecture, particularly enhancer-promoter looping and insulating CTCF-mediated interactions, influences gene transcription in individual cells, which has significant implications for healthy and diseased states. To overcome current limitations in imaging and genomic technologies, we developed a cluster-based phasing strategy using long read nano-NOMe-seq to link distinct CTCF binding states-captured at the single molecule level-to the transcriptional status of genes. By stitching partially overlapping long reads and clustering them by shared GpC-accessibility patterns, we stratify CTCF into graded binding states on individual molecules, classify RNA polymerase states at promoters/gene bodies, and infer when spatial

SUBMITTER: Bellini S 

PROVIDER: S-EPMC12439907 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature