Evolution and genetic architecture of chromatin accessibility and function in yeast. Evolution and genetic architecture of chromatin accessibility and function in yeast

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. Overall design: 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.

染色质开放性（Chromatin accessibility）是一类重要的功能基因组学表型，可调控转录因子结合与基因表达。全基因组尺度技术可实现高分辨率的染色质开放性图谱绘制，助力物种内外染色质结构的遗传架构与演化的精细解析。我们采用甲醛辅助调控元件分离测序（FAIRE-Seq），对两种亲本单倍体酵母物种——酿酒酵母（Saccharomyces cerevisiae）与奇异酵母（Saccharomyces paradoxus）及其二倍体杂交种的染色质开放性进行图谱绘制。研究发现，尽管两类酵母间染色质景观的宏观特征高度保守，但947个基因上游区域的染色质开放性存在显著差异，这些区域富集了细胞内运输、蛋白质定位等基因本体（GO）相关术语。我们还开发了全新的统计方法，用于解析物种间染色质开放性变异的遗传架构，并发现顺式效应（cis effect）较反式效应（trans effect）更为常见且效应量更大。有趣的是，单个基因的顺式与反式效应通常呈负相关，提示存在广泛的补偿性演化以维持染色质开放性水平的稳定。最后，我们证实染色质开放性与基因表达水平间的关系较为复杂，且相当一部分染色质开放性差异可能在功能上无显著影响。

整体实验设计：
本数据集总计包含20个样本。其中10个为FAIRE-Seq样本：具体包括6个单倍体样本，分别为酿酒酵母菌株UWOPS05_217_3的2次生物学重复、酿酒酵母菌株DBVPG1373的2次生物学重复，以及奇异酵母菌株CBS432的2次生物学重复；另有4个二倍体杂交样本，分别为酿酒酵母菌株UWOPS05_217_3与奇异酵母菌株CBS432杂交种的2次生物学重复，以及酿酒酵母菌株DBVPG1373与奇异酵母菌株CBS432杂交种的2次生物学重复。此外，上述10个样本均配有对应的RNA测序（RNA-seq）样本。