Delineation of the DNA Structural Features of Eukaryotic Core Promoter Classes

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.

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“…Transcription carried out by an initiator is usually from a position that overlaps a TSS [ 28 ]. A downstream promoter element (DPE) consensus (A/G-G-A/T-C/T-G/A/C) located +28 to 32 relative to the initiator, was mainly present in core promoters that lack a TATA box motif [ 30 ]. However, no potential DPE element was identified downstream of the putative initiator in the GSTe2 promoter in An.…”

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“…In the next step, a preliminary analysis is essential to convert the TSS level methylation to gene level, focusing specifically on the -6 kb to +3 kb range around transcription start sites (TSS). This range will be subdivided into five distinct regions and probes located outside this specified range will be excluded from the analysis, which will convert rows from the CpG site level to gene-level [33][34][35][36][37] . In detail, promoter regions were delineated into three categories: the core promoter region (0-50bp upstream of TSS), the proximal promoter region (50-250bp upstream of TSS), and the distal promoter region (250-3000bp upstream of TSS).…”

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“…A promoter is a DNA sequence that controls gene expression; it contains binding sites for transcription factors and RNA polymerases [ 19 ]. The number and spectrum of transcription factors involved and the position of their binding sites relative to the transcription start site (TSS) determine the frequency of binding of the transcription complex and, therefore, the efficiency of gene expression that corresponds to such a characteristic of the promoter as “promoter strength” [ 19 , 20 , 21 ]. The versatility or tissue-specificity of a promoter (the ability to provide gene expression in a wide range of cells or in a certain type of them) is ensured by the presence of binding sites for versatile or tissue-specific transcription factors, respectively [ 19 , 20 , 21 ].…”

“…The number and spectrum of transcription factors involved and the position of their binding sites relative to the transcription start site (TSS) determine the frequency of binding of the transcription complex and, therefore, the efficiency of gene expression that corresponds to such a characteristic of the promoter as “promoter strength” [ 19 , 20 , 21 ]. The versatility or tissue-specificity of a promoter (the ability to provide gene expression in a wide range of cells or in a certain type of them) is ensured by the presence of binding sites for versatile or tissue-specific transcription factors, respectively [ 19 , 20 , 21 ]. A constitutively active promoter contains binding sites for transcription factors that are permanently active in a certain cell type, which ensures constant gene expression.…”