In silico discovery of repetitive elements as key sequence determinants of 3D genome folding.

ABSTRACT: Natural and experimental genetic variants can modify DNA loops and insulating boundaries to tune transcription, but it is unknown how sequence perturbations affect chromatin organization genome wide. We developed a deep-learning strategy to quantify the effect of any insertion, deletion, or substitution on chromatin contacts and systematically scored millions of synthetic variants. While most genetic manipulations have little impact, regions with CTCF motifs and active transcription are highly sensitive, as expected. Our unbiased screen and subsequent targeted experiments also point to noncoding RNA genes and several families of repetitive elements as CTCF-motif-free DNA sequences with particularly large effects on nearby chromatin interactions, sometimes exceeding the effects of CTCF site

SUBMITTER: Gunsalus LM 

PROVIDER: S-EPMC10589630 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature