title: Strategies to regulate transcription factor-mediated gene positioning and interchromosomal clustering at the nuclear periphery.
abstract: In budding yeast, targeting of active genes to the nuclear pore complex (NPC) and interchromosomal clustering is mediated by transcription factor (TF) binding sites in the gene promoters. For example, the binding sites for the TFs Put3, Ste12, and Gcn4 are necessary and sufficient to promote positioning at the nuclear periphery and interchromosomal clustering. However, in all three cases, gene positioning and interchromosomal clustering are regulated. Under uninducing conditions, local recruitment of the Rpd3(L) histone deacetylase by transcriptional repressors blocks Put3 DNA binding. This is a general function of yeast repressors: 16 of 21 repressors blocked Put3-mediated subnuclear positioning; 11 of these required Rpd3. In contrast, Ste12-mediated gene positioning is regulated independently of DNA binding by mitogen-activated protein kinase phosphorylation of the Dig2 inhibitor, and Gcn4-dependent targeting is up-regulated by increasing Gcn4 protein levels. These different regulatory strategies provide either qualitative switch-like control or quantitative control of gene positioning over different time scales.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201.
authors.forename: Carlo
authors.initials: C
authors.lastname: Randise-Hinchliff
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201.
authors.forename: Robert
authors.initials: R
authors.lastname: Coukos
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201.
authors.forename: Varun
authors.initials: V
authors.lastname: Sood
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201.
authors.forename: Michael Chas
authors.initials: MC
authors.lastname: Sumner
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zdraljevic
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201.
authors.forename: Lauren
authors.initials: L
authors.lastname: Meldi Sholl
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201.
authors.forename: Donna
authors.initials: D
authors.lastname: Garvey Brickner
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201.
authors.forename: Sara
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201.
authors.forename: Lauren
authors.initials: L
authors.lastname: Watchmaker
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201 j-brickner@northwestern.edu.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Brickner
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000235:genetics*; D016000:Cluster Analysis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D006655:Histone Deacetylases / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics*; D022022:Nuclear Pore / Q000235:genetics*; D010766:Phosphorylation / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors; D006655:Histone Deacetylases