Isaac Sara, Walfridsson Julian, Zohar Tal, Lazar David, Kahan Tamar, Ekwall Karl, Cohen Amikam
Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel 91010.
Genetics. 2007 Apr;175(4):1549-60. doi: 10.1534/genetics.106.068684.
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 alpha-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 approximately 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.
Epe1是一种JmjC结构域蛋白，可拮抗粟酒裂殖酵母中的异染色质化。相关的JmjC结构域蛋白催化一种依赖于Fe(II)和α-酮戊二酸的组蛋白去甲基化反应。然而，未检测到与Epe1相关的去甲基酶活性，并且其JmjC结构域缺乏Fe(II)结合残基的保守性。我们报道Swi6将Epe1招募至异染色质，并且epe1+的过表达，就像沉默基因中的突变或swi6+的过表达一样，会上调某些基因的表达。在epe1+过表达上调的基因列表与组蛋白去乙酰化酶基因突变上调的基因列表之间观察到显著重叠。然而，大多数共同基因不受Clr4组蛋白甲基转移酶的调控。这表明Epe1在组蛋白去乙酰化阶段与异染色质组装途径相互作用。Epe1的突变失活下调了约12%的粟酒裂殖酵母基因，这些基因的列表与沉默基因突变上调的基因列表以及clr6-1突变体中其启动子区域超乙酰化的基因列表有显著重叠。我们提出，抑制性HDACs活性与Epe1之间的相互作用有助于调控粟酒裂殖酵母中的基因表达。
