Institute of Molecular Biology, University of Oregon, Eugene, OR 97403.
Proc Natl Acad Sci U S A. 2024 Aug 6;121(32):e2404770121. doi: 10.1073/pnas.2404770121. Epub 2024 Jul 29.
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 and identified three previously uncharacterized genes that are important for silencing: (), (; ), and (; ). We found that SDS3, RLP1, and RLP2 associate with homologs of the 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 a, and perhaps in other organisms.
在许多生物中，抑制兼性异染色质对于发育过程至关重要。组蛋白 H3 赖氨酸 27（H3K27）的多梳抑制复合物 2 甲基化是真菌和高等真核生物中兼性异染色质的一个显著特征。尽管这种甲基化通常与沉默相关，但抑制的详细机制仍不完全清楚。我们利用正向遗传学方法来鉴定在 中维持兼性异染色质基因沉默所必需的基因，并鉴定了三个以前未被表征的基因，它们对沉默很重要： （）、 （； ）和 （； ）。我们发现 SDS3、RLP1 和 RLP2 与 Rpd3L 复合物的同源物相关联，并且是抑制一组 H3K27 甲基化基因所必需的。这些基因的缺失不会导致 H3K27 甲基化的丧失，但会增加上调基因的组蛋白 H3 赖氨酸 14 的乙酰化，这表明 RPD3L 驱动的去乙酰化是沉默兼性异染色质所必需的因素，这可能在 中，也可能在其他生物体中。
