Single-cell multi-scale footprinting reveals the modular organization of DNA regulatory elements.

ABSTRACT: Cis-regulatory elements control gene expression and are dynamic in their structure, reflecting changes to the composition of diverse effector proteins over time^1-3. Here we sought to connect the structural changes at cis-regulatory elements to alterations in cellular fate and function. To do this we developed PRINT, a computational method that uses deep learning to correct sequence bias in chromatin accessibility data and identifies multi-scale footprints of DNA-protein interactions. We find that multi-scale footprints enable more accurate inference of TF and nucleosome binding. Using PRINT with single-cell multi-omics, we discover wide-spread changes to the structure and function of candidate cis-regulatory elements (cCREs) across hematopoiesis, wherein nuc

SUBMITTER: Hu Y 

PROVIDER: S-EPMC10081223 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature