title: Mechanism of the long range anti-silencing function of targeted histone acetyltransferases in yeast.
abstract: Transcriptionally silent chromatin in Saccharomyces cerevisiae is associated with histone hypoacetylation and is formed through the action of the Sir histone deacetylase complex. A histone acetyltransferase (HAT) targeted near silent chromatin can overcome silencing at a distance by increasing histone acetylation in a sizable region. However, how a tethered HAT acetylates distant nucleosomes has not been resolved. We demonstrate here that targeting the histone H3-specific HAT Gcn5p promotes acetylation of not only histone H3 but also histone H4 in a broad region. We also show that long range anti-silencing and histone acetylation by targeted HATs can be blocked by nucleosome-excluding sequences. These results are consistent with the contention that a tethered HAT promotes stepwise propagation of histone acetylation along the chromatin. Because histone hypoacetylation is key to the formation and maintenance of transcriptionally silent chromatin, it is believed that acetylation promoted by a targeted HAT disrupts silent chromatin thereby overcoming silencing. However, we show that the acetylated and transcriptionally active region created by a tethered HAT retains structural hallmarks of Sir-dependent silent chromatin and remains associated with Sir proteins indicating that tethered HATs overcome silencing without completely dismantling silent chromatin.
authors.affiliation: Department of Biology, University of Rochester, New York 14627, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Yu
authors.forename: Joseph
authors.initials: J
authors.lastname: Sandmeier
authors.forename: Hengping
authors.initials: H
authors.lastname: Xu
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Zou
authors.forename: Xin
authors.initials: X
authors.lastname: Bi
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics; D020868:Gene Silencing; D051548:Histone Acetyltransferases / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D008836:Micrococcal Nuclease / Q000378:metabolism; D009707:Nucleosomes / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D005656:Fungal Proteins; D006657:Histones; D009707:Nucleosomes; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D051548:Histone Acetyltransferases; D008836:Micrococcal Nuclease