Molecular mechanisms enabling the switching and maintenance of epigenetic states are not fully understood. Distinct histone modifications are often associated with ON/OFF epigenetic states, but how these states are stably maintained through DNA replication, yet in certain situations switch from one to another remains unclear. Here, we address this problem through identification of Arabidopsis INCURVATA11 (ICU11) as a Polycomb Repressive Complex 2 accessory protein. ICU11 robustly immunoprecipitated in vivo with PRC2 core components and the accessory proteins, EMBRYONIC FLOWER 1 (EMF1), LIKE HETEROCHROMATIN PROTEIN1 (LHP1), and TELOMERE_REPEAT_BINDING FACTORS (TRBs). ICU11 encodes a 2-oxoglutarate–dependent dioxygenase, an activity associated with histone demethylation in other organisms, and mutant plants show defects in multiple aspects of the Arabidopsis epigenome. To investigate its primary molecular function we identified the Arabidopsis FLOWERING LOCUS C (FLC) as a direct target and found icu11 disrupted the cold-induced, Polycomb-mediated silencing underlying vernalization. icu11 prevented reduction in H3K36me3 levels normally seen during the early cold phase, supporting a role for ICU11 in H3K36me3 demethylation. This was coincident with an attenuation of H3K27me3 at the internal nucleation site in FLC, and reduction in H3K27me3 levels across the body of the gene after plants were returned to the warm. Thus, ICU11 is required for the cold-induced epigenetic switching between the mutually exclusive chromatin states at FLC, from the active H3K36me3 state to the silenced H3K27me3 state. These data support the importance of physical coupling of histone modification activities to promote epigenetic switching between opposing chromatin states.

能够切换和维持表观遗传状态的分子机制尚未完全了解。不同的组蛋白修饰通常与 ON/OFF 表观遗传状态相关，但这些状态如何通过 DNA 复制稳定维持，但在某些情况下从一种状态切换到另一种状态仍不清楚。在这里，我们通过鉴定拟南芥INCURVATA11 (ICU11) 作为多梳抑制复合物 2 辅助蛋白来解决这个问题。 ICU11 在体内与 PRC2 核心成分和辅助蛋白、胚胎花 1 (EMF1)、异染色质蛋白样蛋白 1 (LHP1) 和端粒重复结合因子 (TRB) 进行强力免疫沉淀。 ICU11编码一种 2-酮戊二酸依赖性双加氧酶，这是一种与其他生物体中组蛋白去甲基化相关的活性，突变植物在拟南芥表观基因组的多个方面表现出缺陷。为了研究其主要分子功能，我们将拟南芥开花基因座 C ( FLC ) 确定为直接靶标，并发现icu11破坏了寒冷诱导的、Polycomb 介导的春化沉默。 icu11阻止了通常在寒冷早期阶段出现的 H3K36me3 水平降低，支持了 ICU11 在 H3K36me3 去甲基化中的作用。这与FLC内部成核位点的 H3K27me3 减弱以及植物恢复温暖后整个基因体内 H3K27me3 水平的降低相一致。因此，冷诱导的FLC染色质状态之间的表观遗传转换需要 ICU11，从活跃的 H3K36me3 状态到沉默的 H3K27me3 状态。 这些数据支持组蛋白修饰活性的物理耦合对于促进相反染色质状态之间的表观遗传转换的重要性。