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首页> 外文期刊>PLoS Genetics >Kicking against the PRCs 鈥?A Domesticated Transposase Antagonises Silencing Mediated by Polycomb Group Proteins and Is an Accessory Component of Polycomb Repressive Complex 2
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Kicking against the PRCs 鈥?A Domesticated Transposase Antagonises Silencing Mediated by Polycomb Group Proteins and Is an Accessory Component of Polycomb Repressive Complex 2

机译:抵制中华人民共和国的“驯化的转座酶拮抗”,这是由Polycomb组蛋白介导的沉默,是Polycomb Repressive Complex 2的辅助成分

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The Polycomb group (PcG) and trithorax group (trxG) genes play crucial roles in development by regulating expression of homeotic and other genes controlling cell fate. Both groups catalyse modifications of chromatin, particularly histone methylation, leading to epigenetic changes that affect gene activity. The trxG antagonizes the function of PcG genes by activating PcG target genes, and consequently trxG mutants suppress PcG mutant phenotypes. We previously identified the ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN1 (ALP1) gene as a genetic suppressor of mutants in the Arabidopsis PcG gene LIKE HETEROCHROMATIN PROTEIN1 (LHP1). Here, we show that ALP1 interacts genetically with several other PcG and trxG components and that it antagonizes PcG silencing. Transcriptional profiling reveals that when PcG activity is compromised numerous target genes are hyper-activated in seedlings and that in most cases this requires ALP1. Furthermore, when PcG activity is present ALP1 is needed for full activation of several floral homeotic genes that are repressed by the PcG. Strikingly, ALP1 does not encode a known chromatin protein but rather a protein related to PIF/Harbinger class transposases. Phylogenetic analysis indicates that ALP1 is broadly conserved in land plants and likely lost transposase activity and acquired a novel function during angiosperm evolution. Consistent with this, immunoprecipitation and mass spectrometry (IP-MS) show that ALP1 associates, in vivo, with core components of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a widely conserved PcG protein complex which functions as a H3K27me3 histone methyltransferase. Furthermore, in reciprocal pulldowns using the histone methyltransferase CURLY LEAF (CLF), we identify not only ALP1 and the core PRC2 components but also plant-specific accessory components including EMBRYONIC FLOWER 1 (EMF1), a transcriptional repressor previously associated with PRC1-like complexes. Taken together our data suggest that ALP1 inhibits PcG silencing by blocking the interaction of the core PRC2 with accessory components that promote its HMTase activity or its role in inhibiting transcription. ALP1 is the first example of a domesticated transposase acquiring a novel function as a PcG component. The antagonistic interaction of a modified transposase with the PcG machinery is novel and may have arisen as a means for the cognate transposon to evade host surveillance or for the host to exploit features of the transposition machinery beneficial for epigenetic regulation of gene activity.
机译:Polycomb组(PcG)和trithorax组(trxG)基因通过调节同源基因和其他控制细胞命运的基因的表达在发育中起关键作用。两组均催化染色质的修饰,特别是组蛋白甲基化,从而导致影响基因活性的表观遗传学变化。 trxG通过激活PcG靶基因来拮抗PcG基因的功能,因此trxG突变体会抑制PcG突变体表型。我们以前鉴定出类似拟南芥色素蛋白1(ALP1)的拮抗剂作为拟南芥PcG基因类似异种色素蛋白1(LHP1)中突变体的遗传抑制剂。在这里,我们显示ALP1与其他几个PcG和trxG成分发生了遗传相互作用,并且拮抗了PcG沉默。转录谱分析显示,当PcG活性受到损害时,许多靶基因在幼苗中被过度激活,并且在大多数情况下,这需要ALP1。此外,当存在PcG活性时,需要ALP1才能完全激活被PcG抑制的几种花卉同源基因。令人惊讶的是,ALP1不编码已知的染色质蛋白,而是编码与PIF / Harbinger类转座酶有关的蛋白。系统发育分析表明,ALP1在陆地植物中广泛保存,可能丢失转座酶活性,在被子植物的进化过程中获得了新的功能。与此相一致,免疫沉淀和质谱法(IP-MS)显示,ALP1在体内与POLYCOMB REPRESSIVE COMPLEX 2(PRC2)的核心成分相关联,POLYCOMB REPRESSIVE COMPLEX 2(PRC2)是一种广泛保存的PcG蛋白复合物,其功能为H3K27me3组蛋白甲基转移酶。此外,在使用组蛋白甲基转移酶CURLY LEAF(CLF)进行的双向下拉反应中,我们不仅鉴定了ALP1和核心PRC2组分,而且鉴定了植物特异性辅助组分,包括EMBRYONIC FLOWER 1(EMF1),EMBRYONIC FLOWER 1(EMF1),一种先前与PRC1样复合物相关的转录阻遏物。汇总我们的数据表明,ALP1通过阻止核心PRC2与促进其HMTase活性或其抑制转录作用的辅助成分的相互作用来抑制PcG沉默。 ALP1是获得新型功能作为PcG组件的驯化转座酶的第一个例子。修饰的转座酶与PcG机制的拮抗相互作用是新颖的,并且可能作为同源转座子逃避宿主监视或使宿主利用有利于基因活性的表观遗传调控的转座机制的特征而出现。

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