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Abstract：
Repression of facultative heterochromatin is essential for developmental processes in numerous organisms. Methylation of histone H3 lysine 27 (H3K27) by Polycomb repressive complex 2 is a prominent feature of facultative heterochromatin in both fungi and higher eukaryotes. Although this methylation is frequently associated with silencing, the detailed mechanism of repression remains incompletely understood. We utilized a forward genetics approach to identify genes required to maintain silencing at facultative heterochromatin genes in Neurospora crassa and identified three previously uncharacterized genes that are important for silencing: sds3 (NCU01599), rlp1 (RPD3L protein 1; NCU09007), and rlp2 (RPD3L protein 2; NCU02898). We found that SDS3, RLP1, and RLP2 associate with N. crassa homologs of the Saccharomyces cerevisiae Rpd3L complex and are required for repression of a subset of H3K27-methylated genes. Deletion of these genes does not lead to loss of H3K27 methylation but increases acetylation of histone H3 lysine 14 at up-regulated genes, suggesting that RPD3L-driven deacetylation is a factor required for silencing of facultative heterochromatin in N. crassa, and perhaps in other organisms.
摘要：
抑制兼性异染色质对于许多生物体的发育过程至关重要。Polycomb抑制复合物2对组蛋白H3赖氨酸27（H3K27）的甲基化是真菌和高等真核生物兼性异染色质的显着特征。尽管这种甲基化通常与沉默有关，压制的详细机制仍未完全理解。我们利用正向遗传学方法来鉴定在粗糙神经孢菌中维持兼性异染色质基因沉默所需的基因，并鉴定了三个以前未表征的对沉默很重要的基因：sds3（NCU01599），rlp1（RPD3L蛋白1；NCU09007），和rlp2(RPD3L蛋白2;NCU02898)。我们发现SDS3，RLP1和RLP2与酿酒酵母Rpd3L复合物的N.crassa同源物相关，并且是抑制H3K27甲基化基因子集所必需的。这些基因的缺失不会导致H3K27甲基化的缺失，但会增加组蛋白H3赖氨酸14在上调基因的乙酰化，这表明RPD3L驱动的脱乙酰是N.crassa中兼性异染色质沉默所需的因素，也许在其他生物体中。
