Dissecting the <i>cis</i>-regulatory syntax of transcription initiation with deep learning.

ABSTRACT: Despite extensive characterization of mammalian Pol II transcription, the DNA sequence determinants of transcription initiation at a third of human promoters and most enhancers remain poorly understood. We trained and interpreted a neural network called ProCapNet that accurately models base-resolution initiation profiles from PRO-cap experiments using local DNA sequence. ProCapNet learns sequence motifs with distinct effects on initiation rates and TSS positioning and uncovers context-specific cryptic initiator elements intertwined within other TF motifs. ProCapNet annotates predictive motifs in nearly all actively transcribed regulatory elements across multiple cell-lines, revealing a shared cis-regulatory logic across promoters and enhancers and a highly epistatic sequence syntax

SUBMITTER: Cochran K 

PROVIDER: S-EPMC11160661 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature