Abstract
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.
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Acknowledgements
We thank D. Gottschling, K. Nasmyth and J. Rine for plasmids and yeast strains; H. Araki, M. Grunstein, C. L. Peterson and K. Struhl for the protocols for the ChrIP assay; S. Harashima and Y. Ohya for tools and advice on yeast manipulation; K. Hasegawa, Y. Ikejiri, K. Matsubara, S. Okano, T. Sakuno and S. Yoshihara for technical assistance; and T. Suzuki, M. Yamaki and all members of our laboratory for discussions and comments on the manuscript. A.K. is a Research Fellow of the Japan Society for the Promotion of Science. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by Exploratory Research for Advanced Technology of the Japan Science and Technology Corporation.
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Kimura, A., Umehara, T. & Horikoshi, M. Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing. Nat Genet 32, 370–377 (2002). https://doi.org/10.1038/ng993
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DOI: https://doi.org/10.1038/ng993
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