title: Developmentally induced changes in transcriptional program alter spatial organization across chromosomes.
abstract: Although the spatial location of genes within the nucleus has been implicated in their transcriptional status, little is known about the dynamics of gene location that accompany large-scale changes in gene expression. The mating of haploid yeast Saccharomyces cerevisiae is accompanied by a large-scale change in transcription and developmental program. We examined changes in nuclear organization that accompany stimulus by the mating pheromone alpha factor and found that most alpha-factor-induced genes become associated with components of the nuclear envelope. The myosin-like protein Mlp1, which has been implicated in mRNA export, was further shown to exhibit RNA dependence in its association with alpha-factor-induced genes. High-resolution mapping of association of chromosome III with Mlp1 revealed alpha-factor-dependent determinants of nuclear pore association, including origins of replication, specific intergenic regions, and the 3' ends of transcriptionally activated genes. Taken together, these results reveal RNA- and DNA-dependent determinants of nuclear organization as well as a detailed picture of how an entire chromosome alters its spatial conformation in response to a developmental cue.
authors.affiliation: Department of Systems Biology, Harvard Medical School and The Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Casolari
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Brown
authors.forename: David A
authors.initials: DA
authors.lastname: Drubin
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rando
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Silver
mesh_terms: D015825:Chromosomes, Fungal / Q000502:physiology*; D021901:DNA, Intergenic / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000235:genetics / Q000502:physiology*; D022022:Nuclear Pore / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D018741:Replication Origin / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
chemical_list: D021901:DNA, Intergenic; C048632:MF(ALPHA)1 protein, S cerevisiae; C080988:MLP1 protein, S cerevisiae; D009687:Nuclear Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins