The PEAT protein complexes are required for histone deacetylation and heterochromatin silencing

In eukaryotes, heterochromatin regions are typically subjected to transcriptional silencing. DNA methylation has an important role in such silencing, and has been studied extensively. However, little is known about how methylated heterochromatin regions are subjected to silencing. We conducted a genetic screen and identified an epcr (enhancer of polycomb-related) mutant that releases heterchromatin silencing in Arabidopsis thaliana. We demonstrated that EPCR1 functions redundantly with its paralog EPCR2 and interacts with PWWP domain-containing proteins (PWWPs), AT-rich interaction domain-containing proteins (ARIDs), and telomere repeat binding proteins (TRBs), thus forming multiple functionally redundant protein complexes named PEAT (PWWPs-EPCRs-ARIDs-TRBs). The PEAT complexes mediate histone deacetylation and heterochromatin condensation and thereby facilitate heterochromatin silencing. In heterochromatin regions, the production of small interfering RNAs (siRNAs) and DNA methylation are repressed by the PEAT complexes. The study reveals how histone deacetylation, heterochromatin condensation, siRNA production, and DNA methylation interplay with each other and thereby maintain heterochromatin silencing.

在真核生物中，异染色质区域通常处于转录沉默状态。DNA甲基化在这类转录沉默过程中发挥关键作用，且已被广泛研究。然而，目前对于甲基化异染色质区域如何实现转录沉默的具体机制仍知之甚少。本研究通过遗传筛选，在拟南芥中鉴定到一株可解除异染色质沉默的epcr（enhancer of polycomb-related，多梳相关增强因子）突变体。本研究证实，EPCR1与其旁系同源基因EPCR2存在功能冗余，并可与含PWWP结构域的蛋白（PWWPs）、含AT富集结合结构域的蛋白（ARIDs）以及端粒重复序列结合蛋白（TRBs）相互作用，进而形成多个功能冗余的蛋白质复合物，命名为PEAT（PWWPs-EPCRs-ARIDs-TRBs）。PEAT复合物可介导组蛋白去乙酰化与异染色质凝聚，从而促进异染色质沉默的维持。在异染色质区域中，PEAT复合物会抑制小干扰RNA（siRNAs）的生成与DNA甲基化过程。本研究揭示了组蛋白去乙酰化、异染色质凝聚、小干扰RNA生成与DNA甲基化之间的相互调控关系，从而阐明了异染色质沉默的维持机制。