Delineation of the DNA Structural Features of Eukaryotic Core Promoter Classes

ACS Omega. 2022 Feb 9;7(7):5657-5669. doi: 10.1021/acsomega.1c04603. eCollection 2022 Feb 22.

Abstract

The eukaryotic transcription is orchestrated from a chunk of the DNA region stated as the core promoter. Multifarious and punctilious core promoter signals, viz., TATA-box, Inr, BREs, and Pause Button, are associated with a subset of genes and regulate their spatiotemporal expression. However, the core promoter architecture linked with these signals has not been investigated exhaustively for several species. In this study, we attempted to envisage the adaptive binding landscape of the transcription initiation machinery as a function of DNA structure. To this end, we deployed a set of k-mer based DNA structural estimates and regular expression models derived from experiments, molecular dynamic simulations, and theoretical frameworks, and high-throughout promoter data sets retrieved from the eukaryotic promoter database. We categorized protein-coding gene core promoters based on characteristic motifs at precise locations and analyzed the B-DNA structural properties and non-B-DNA structural motifs for 15 different eukaryotic genomes. We observed that Inr, BREd, and no-motif classes display common patterns of DNA sequence and structural environment. TATA-containing, BREu, and Pause Button classes show a deviant behavior with the TATA class displaying varied axial and twisting flexibility while BREu and Pause Button leaned toward G-quadruplex motif enrichment. Intriguingly, DNA meltability and shape signals are conserved irrespective of the presence or absence of distinct core promoter motifs in the majority of species. Altogether, here we delineated the conserved DNA structural signals associated with several promoter classes that may contribute to the chromatin configuration, orchestration of transcription machinery, and DNA duplex melting during the transcription process.