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Genomic environments scale the activities of diverse core promoters.

ABSTRACT: A classical model of gene regulation is that enhancers provide specificity whereas core promoters provide a modular site for the assembly of the basal transcriptional machinery. However, examples of core promoter specificity have led to an alternate hypothesis in which specificity is achieved by core promoters with different sequence motifs that respond differently to genomic environments containing different enhancers and chromatin landscapes. To distinguish between these models, we measured the activities of hundreds of diverse core promoters in four different genomic locations and, in a complementary experiment, six different core promoters at thousands of locations across the genome. Although genomic locations had large effects on expression, the intrinsic activities of different classes of promoters were preserved across genomic locations, suggesting that core promoters are modular regulatory elements whose activities are independently scaled up or down by different genomic locations. This scaling of promoter activities is nonlinear and depends on the genomic location and the strength of the core promoter. Our results support the classical model of regulation in which diverse core promoter motifs set the intrinsic strengths of core promoters, which are then amplified or dampened by the activities of their genomic environments.

SUBMITTER: Hong CKY

PROVIDER: S-EPMC8744677 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Genomic environments scale the activities of diverse core promoters

Project description:One model for how cells integrate cis-regulatory information is that housekeeping and developmental core promoters respond specifically to certain types of enhancers or chromatin features at different chromosomal locations. We tested this model using a genome-integrated massively parallel reporter assay (MPRA) to measure the activity of hundreds of diverse core promoters at four genomic locations While genomic locations had large effects on expression, the relative strengths of core promoters were preserved across locations regardless of promoter class, suggesting that their intrinsic activities are scaled at different genomic locations. We further show that core promoter scaling is a genome-wide phenomenon by testing six core promoters at thousands of locations across the genome. While the rank order of core promoters is preserved, the scaling of expression across the genome is non-linear and depends on the genomic location and the strength of the core promoter, but not on its class, suggesting that housekeeping and developmental promoters do not make different interactions with the surrounding genomic environment. Instead, our results support a modular genome in which genomic environments containing different enhancers and chromatin features scale the activities of core promoters in an independent, but non-linear manner.

2021-05-01 | GSE173678 | GEO

Genomic environments scale the activities of diverse core promoters

Project description:Genomic environments scale the activities of diverse core promoters

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Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

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Genome wide analysis of Arabidopsis core promoters.

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Fast evolution of core promoters in primate genomes.

Project description:Despite much interest in regulatory evolution, how promoters have evolved remains poorly studied, mainly owing to paucity of data on promoter regions. Using a new set of high-quality experimentally determined core promoters of the human genome, we conducted a comparative analysis of 2,492 human and rhesus macaque promoters and their neighboring nearly neutral regions. We found that the core promoters have an average rate of nucleotide substitution substantially higher than that at 4-fold degenerate sites and only slightly lower than that for the assumed neutral controls of neighboring noncoding regions, suggesting that core promoters are subject to very weak selective constraints. Interestingly, we identified 24 core promoters (at false discovery rate = 50%) that have evolved at an accelerated rate compared with the neutral controls, suggesting that they may have undergone positive selection. The inferred positively selected genes show strong bias in molecular function. We also used population genetic approaches to examine the evolution of core promoters in human populations and found evidence of positive selection at some loci. Taken together, our results suggest that positive selection has played a substantial role in the evolution of transcriptional regulation in primates.

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2007-06-04 | E-MEXP-1090 | biostudies-arrayexpress

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