Genetic landscape of open chromatin in yeast

• Published in: PLoS genetics 2013-02, Vol.9 (2), p.e1003229-e1003229
• Main Authors: Lee, Kibaick, Kim, Sang Cheol, Jung, Inkyung, Kim, Kwoneel, Seo, Jungmin, Lee, Heun-Sik, Bogu, Gireesh K, Kim, Dongsup, Lee, Sanghyuk, Lee, Byungwook, Choi, Jung Kyoon
• Format: Article
• Language: English
• Subjects: Base Sequence; Binding Sites; Biology; Chromatin; Chromatin - genetics; Chromatin - metabolism; Chromosome Mapping; Deoxyribonucleic acid; DNA; DNA methylation; DNA sequencing; Gene Expression Regulation, Fungal; Genetic screening; Genetic variation; Genomics; Health aspects; Methods; Nucleotide sequencing; Oligonucleotide Array Sequence Analysis; Phenotype; Physiological aspects; Proteins; Quantitative genetics; Quantitative trait loci; Quantitative Trait Loci - genetics; Regulatory Sequences, Nucleic Acid - genetics; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Telomere - genetics; Transcription Factors - genetics; Transcription Factors - metabolism; Yeast
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1003229

Chromatin regulation underlies a variety of DNA metabolism processes, including transcription, recombination, repair, and replication. To perform a quantitative genetic analysis of chromatin accessibility, we obtained open chromatin profiles across 96 genetically different yeast strains by FAIRE (formaldehyde-assisted isolation of regulatory elements) assay followed by sequencing. While 5∼10% of open chromatin region (OCRs) were significantly affected by variations in their underlying DNA sequences, subtelomeric areas as well as gene-rich and gene-poor regions displayed high levels of sequence-independent variation. We performed quantitative trait loci (QTL) mapping using the FAIRE signal for each OCR as a quantitative trait. While individual OCRs were associated with a handful of specific genetic markers, gene expression levels were associated with many regulatory loci. We found multi-target trans-loci responsible for a very large number of OCRs, which seemed to reflect the widespread influence of certain chromatin regulators. Such regulatory hotspots were enriched for known regulatory functions, such as recombinational DNA repair, telomere replication, and general transcription control. The OCRs associated with these multi-target trans-loci coincided with recombination hotspots, telomeres, and gene-rich regions according to the function of the associated regulators. Our findings provide a global quantitative picture of the genetic architecture of chromatin regulation.