Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing.
Genes located in chromosomal regions near telomeres are transcriptionally silent, whereas those located in regions away from telomeres are not. Here we show that there is a gradient of acetylation of histone H4 at lysine 16 (H4-Lys16) along a yeast chromosome; this gradient ranges from a hypoacetylated state in regions near the telomere to a hyperacetylated state in more distant regions. The hyperacetylation is regulated by Sas2p, a member of the MYST-type family of histone acetylases, whereas hypoacetylation is under the control of Sir2p, a histone deacetylase. Loss of hyperacetylation is accompanied by an increase in localization of the telomere protein Sir3p and the inactivation of gene expression in telomere-distal regions. Thus, the Sas2p and Sir2p function in concert to regulate transcription in yeast, by acetylating and deacetylating H4-Lys16 in a mechanism that may be common to all eukaryotes.
Kimura
Akatsuki
A
. Horikoshi Gene Selector Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, 5-9-6 Tokodai, Tsukuba, Ibaraki 300-2635, Japan.
Umehara
Takashi
T
Horikoshi
Masami
M
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015153:Blotting, Western; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism* / Q000648:ultrastructure; D017353:Gene Deletion; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005800:Genes, Fungal; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D008954:Models, Biological; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000502:physiology*; D016615:Telomere / Q000648:ultrastructure; D013696:Temperature
D002843:Chromatin; D006657:Histones; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C469266:Sas2 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D008239:Lysine