Project description:Variation in transcriptional regulation is thought to be a major cause of phenotypic diversity. Although widespread differences in gene expression among individuals of a species have been observed, studies to examine the variability of transcription factor binding on a global scale have not been performed, and thus the extent and underlying genetic basis of transcription factor binding diversity is unknown. By mapping differences in transcription factor binding among individuals, here we present the genetic basis of such variation on a genome-wide scale. Whole-genome Ste12-binding profiles were determined using chromatin immunoprecipitation coupled with DNA sequencing in pheromone-treated cells of 43 segregants of a cross between two highly diverged yeast strains and their parental lines. We identified extensive Ste12-binding variation among individuals, and mapped underlying cis- and trans-acting loci responsible for such variation. We showed that most transcription factor binding variation is cis-linked, and that many variations are associated with polymorphisms residing in the binding motifs of Ste12 as well as those of several proposed Ste12 cofactors. We also identified two trans-factors, AMN1 and FLO8, that modulate Ste12 binding to promoters of more than ten genes under alpha-factor treatment. Neither of these two genes was previously known to regulate Ste12, and we suggest that they may be mediators of gene activity and phenotypic diversity. Ste12 binding strongly correlates with gene expression for more than 200 genes, indicating that binding variation is functional. Many of the variable-bound genes are involved in cell wall organization and biogenesis. Overall, these studies identified genetic regulators of molecular diversity among individuals and provide new insights into mechanisms of gene regulation.

| S-EPMC2941147 | biostudies-literature

Survey of transcription factor binding sites in yeast using ChIP-seq

Project description:Survey of transcription factor binding sites in yeast using ChIP-seq

| PRJEB2327 | ENA

Genetic Analysis of Variation in Transcription Factor Binding in Yeast

Project description:This SuperSeries is composed of the SubSeries listed below.

2010-02-18 | GSE19636 | GEO

Natural genetic variation in yeast longevity

Project description:A quantitative genetic analysis of the yeast replicative life span was carried out by sampling the natural genetic variation Genomic DNA was extracted from 39 recombinant lines from a cross between strains S96 and YJM 789.

2012-07-17 | E-GEOD-37590 | biostudies-arrayexpress

ChIP-Seq of yeast to survey transcription factor binding sites

Project description:An experiment was performed to determine the transcription factor binding site of yeast at room temperature.

2011-10-13 | E-MTAB-440 | biostudies-arrayexpress

Rare genetic variation at transcription factor binding site modulates local DNA methylation profiles

Project description:Recently, it has been proposed that local DNA methylation profiles might be dictated by cis-regulatory DNA sequences that mainly operate via DNA-binding factors. Combining blood genome-wide DNA methylation profiles (Illumina Infinium MethylationEPIC BeadChiP), whole genome sequencing-derived single nucleotide variants (SNVs) along with predicted transcription factor binding site (TFBS), we were able to observe that rare regulatory variants, i.e, SNVs that disrupt TFBSs, are associated with DNA methylation at both local and, to a lesser extent, broader locations. Interestingly, we also observed that this directed DNA methylation can have consequences on genome regulation by altering expression levels of nearby genes.

2020-10-24 | GSE159930 | GEO

Skipper analysis of RNA-protein interactions highlights depletion of genetic variation in translation factor binding sites

Project description:Technology for crosslinking and immunoprecipitation followed by sequencing (CLIP-seq) has identified the transcriptomic targets of hundreds of RNA-binding proteins in cells. To improve the power of existing and future CLIP-seq datasets, we introduce Skipper, an end-to-end workflow that converts unprocessed reads into annotated binding sites using an improved statistical framework. Compared to existing methods, Skipper on average calls 3.1-4.2 times more transcriptomic binding sites and sometimes >10 times more sites, providing deeper insight into post-transcriptional gene regulation. Skipper also calls binding to annotated repetitive elements and identifies bound elements for 99% of enhanced CLIP experiments. We perform nine translation factor enhanced CLIPs and apply Skipper to learn determinants of translation factor occupancy including transcript region, sequence, and subcellular localization. Furthermore, we observe depletion of genetic variation in occupied sites and nominate transcripts subject to selective constraint because of translation factor occupancy. Skipper offers fast, easy, customizable analysis of CLIP-seq data.

2022-10-08 | GSE213867 | GEO

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