Non-linear relationship between chromatin accessibility and estradiol-regulated gene expression
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PROVIDER: PRJNA604072 | ENA |
REPOSITORIES: ENA
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Project description:Chromatin accessibility is central to basal and inducible gene expression. Through ATAC-seq experiments in Estrogen Receptor-positive (ER+) breast cancer cell line MCF-7 and integrationvwith multi-omics data, we found that estradiol (E2) induced chromatin accessibility changes in the widely studied E2-regulated genes. As expected, open chromatin regions associated with E2-inducible gene expression showed enrichment of estrogen response element and those associated with E2-repressible gene expression were enriched for PBX1, PBX3, and ERE. Surprisingly, a significant number of E2-inducible genes displayed closed promoters/enhancers and these were enriched for binding for transcription factors such as NF-Y, FOXA1, GRHL2, and BATF, which are known to interact with nucleosomes. While a significant number of open chromatin regions showed FOXA1 occupancy in the absence of E2, E2-treatment further enhanced FOXA1 occupancy suggesting that ER-E2 enhances chromatin occupancy of FOXA1 to a subset of E2-regulated genes. In summation, our results reveal complex mechanisms of ER-E2 interaction with nucleosomes.
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Project description:Chromatin accessibility is an important functional genomics phenotype that influences transcription factor binding and gene expression. Genome-scale technologies allow chromatin accessibility to be mapped with high-resolution, facilitating detailed analyses into the genetic architecture and evolution of chromatin structure within and between species. We performed Formaldehyde-Assisted Isolation of Regulatory Elements sequencing (FAIRE-Seq) to map chromatin accessibility in two parental haploid yeast species, Saccharomyces cerevisiae and Saccharomyces paradoxus and their diploid hybrid. We show that although broad-scale characteristics of the chromatin landscape are well conserved between these species, accessibility is significantly different for 947 regions upstream of genes that are enriched for GO terms such as intracellular transport and protein localization exhibit. We also develop new statistical methods to investigate the genetic architecture of variation in chromatin accessibility between species, and find that cis effects are more common and of greater magnitude than trans effects. Interestingly, we find that cis and trans effects at individual genes are often negatively correlated, suggesting widespread compensatory evolution to stabilize levels of chromatin accessibility. Finally, we demonstrate that the relationship between chromatin accessibility and gene expression levels is complex, and a significant proportion of differences in chromatin accessibility might be functionally benign. There are 20 samples in total. These consist of 10 FAIRE-seq samples, specifically 6 haploid samples, S. cerevisiae strain UWOPS05_217_3 replicates 1 and 2, S. cerevisiae strain DBVPG1373 replicates 1 and 2, and S. paradoxus strain CBS432 replicates 1 and 2. There are also 4 diploid hybrid samples, hybrid between S. cerevisiae strain UWOPS05_217_3 and S. paradoxus strain CBS432 replicates 1 and 2, and the hybrid between S. cerevisiae strain DBVPG1373 and S. paradoxus strain CBS432 replicates 1 and 2. There are also RNA-seq samples for each of these 10 samples.
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