title: Decoupling epigenetic and genetic effects through systematic analysis of gene position.
abstract: Classic "position-effect" experiments repositioned genes near telomeres to demonstrate that the epigenetic landscape can dramatically alter gene expression. Here, we show that systematic gene knockout collections provide an exceptional resource for interrogating position effects, not only near telomeres but at every genetic locus. Because a single reporter gene replaces each deleted gene, interrogating this reporter provides a sensitive probe into different chromatin environments while controlling for genetic context. Using this approach, we find that, whereas systematic replacement of yeast genes with the kanMX marker does not perturb the chromatin landscape, chromatin differences associated with gene position account for 35% of kanMX activity. We observe distinct chromatin influences, including a Set2/Rpd3-mediated antagonistic interaction between histone H3 lysine 36 trimethylation and the Rap1 transcriptional activation site in kanMX. This interaction explains why some yeast genes have been resistant to deletion and allows successful generation of these deletion strains through the use of a modified transformation procedure. These findings demonstrate that chromatin regulation is not governed by a uniform "histone code" but by specific interactions between chromatin and genetic factors.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Menzies
authors.initials: M
authors.lastname: Chen
authors.forename: Katherine
authors.initials: K
authors.lastname: Licon
authors.forename: Rei
authors.initials: R
authors.lastname: Otsuka
authors.forename: Lorraine
authors.initials: L
authors.lastname: Pillus
authors.forename: Trey
authors.initials: T
authors.lastname: Ideker
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000378:metabolism; D055012:Chromosomal Position Effects / Q000235:genetics*; D015825:Chromosomes, Fungal / Q000235:genetics; D004171:Diploidy; D044127:Epigenesis, Genetic; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D015723:Gene Library; D023061:Gene Order / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics; D005819:Genetic Markers; D006579:Heterozygote; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D016254:Mutagenesis, Insertional / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D002843:Chromatin; D005819:Genetic Markers; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D008239:Lysine