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Genetics, Vol. 175, 1549-1560, April 2007, Copyright © 2007
doi:10.1534/genetics.106.068684
Interaction of Epe1 With the Heterochromatin Assembly Pathway in Schizosaccharomyces pombe
Sara Isaac*,1,
Julian Walfridsson
,1,
Tal Zohar*,
David Lazar*,
Tamar Kahan
,
Karl Ekwall and
Amikam Cohen*,2
* Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel 91010, Department of Biosciences, Karolinska Institute, and University College Södertörn, S-141 89 Huddinge, Sweden and Bioinformatic Unit, The Hebrew University-Hadassah Medical School, Jerusalem, Israel 91010
2 Corresponding author: Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel 91010.
E-mail: amikamc{at}cc.huji.ac.il
Epe1 is a JmjC domain protein that antagonizes heterochromatization in Schizosaccharomyces pombe. Related JmjC domain proteins catalyze a histone demethylation reaction that depends on Fe(II) and 
-ketoglutarate. However, no detectable demethylase activity is associated with Epe1, and its JmjC domain lacks conservation of Fe(II)-binding residues. We report that Swi6 recruits Epe1 to heterochromatin and that overexpression of epe1+, like mutations in silencing genes or overexpression of swi6+, upregulates expression of certain genes. A significant overlap was observed between the lists of genes that are upregulated by overexpression of epe1+ and those that are upregulated by mutations in histone deacetylase genes. However, most of the common genes are not regulated by Clr4 histone methyltransferase. This suggests that Epe1 interacts with the heterochromatin assembly pathway at the stage of histone deacetylation. Mutational inactivation of Epe1 downregulates 
12% of S. pombe genes, and the list of these genes overlaps significantly with the lists of genes that are upregulated by mutations in silencing genes and genes that are hyperacetylated at their promoter regions in clr6-1 mutants. We propose that an interplay between the repressive HDACs activity and Epe1 helps to regulate gene expression in S. pombe.
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Genetics 2007 175: NP.