Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer.
Researchers identified 3,216 prostate cancer-specific enhancers through chromatin analysis.
Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer.
The transcription process is controlled by non-coding regulatory elements, more than 70% of which are putative enhancers.
Ultra-high-resolution chromatin interaction profiling by Region Capture Micro-C at a representative chr6q24.1 locus reveals that these enhancers form cancer-specific, highly nested interactions with promoters that coalesce into a multi-connected hub absent in normal prostate cells.
CRISPR/Cas9 perturbations of these enhancers, examined one by one, distinguish enhancer classes within the hub.
We also observe that FOXA1, a pioneer transcription factor activated in prostate cancer, directly binds to these enhancers and regulates distinct enhancer classes, leading to varying degrees of chromatin accessibility and gene expression changes.
These findings suggest that enhancers function in a coordinated manner, forming multi-connected cancer-specific chromatin interaction hubs, with distinct enhancer classes contributing differently to gene regulation.
This study advances our ability to modulate gene expression in a cell type-specific manner, opening new avenues for precision therapies.