Kicking against the PRCs - A Domesticated Transposase Antagonises Silencing Mediated by Polycomb Group Proteins and Is an Accessory Component of Polycomb Repressive Complex 2.
Kicking against the PRCs - A Domesticated Transposase Antagonises Silencing Mediated by Polycomb Group Proteins and Is an Accessory Component of Polycomb Repressive Complex 2.
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DOI：
10.1371/journal.pgen.1005660
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发表时间：
2015-12
期刊：
影响因子：
4.5
通讯作者：
Goodrich J
中科院分区：
文献类型：
--
作者：
Liang SC;Hartwig B;Perera P;Mora-García S;de Leau E;Thornton H;de Lima Alves F;Rappsilber J;Yang S;James GV;Schneeberger K;Finnegan EJ;Turck F;Goodrich J
多梳组（PcG）和三胸组（trxG）基因通过调节同源异型和其他控制细胞命运的基因的表达在发育中起着至关重要的作用。这两组催化染色质的修饰，特别是组蛋白甲基化，导致影响基因活性的表观遗传变化。trxG通过激活PcG靶基因拮抗PcG基因的功能，因此trxG突变体抑制PcG突变体表型。我们先前鉴定了类异染色质蛋白1（ALP 1）基因拮抗剂作为拟南芥PcG基因类异染色质蛋白1（LHP 1）突变体的遗传抑制因子。在这里，我们表明，ALP 1与其他几个PcG和trxG组件的遗传相互作用，它拮抗PcG沉默。转录谱显示，当PcG活性受损时，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ALP 1。此外，当PcG活性存在时，需要ALP 1来完全激活被PcG抑制的几个花同源异型基因。引人注目的是，ALP 1不编码已知的染色质蛋白，而是与PIF/Harbinger类转座酶相关的蛋白。系统发育分析表明，ALP 1在陆地植物中广泛保守，可能在被子植物进化过程中失去了转座酶活性并获得了新的功能。与此一致，免疫沉淀和质谱（IP-MS）显示，ALP 1在体内与多梳抑制复合物2（PRC 2）的核心组分相关，PRC 2是一种广泛保守的PcG蛋白复合物，其功能为H3 K27 me 3组蛋白甲基转移酶。此外，在使用组蛋白甲基转移酶卷曲叶（CLF）的相互下拉中，我们不仅确定了ALP 1和核心PRC 2组件，而且还确定了植物特异性辅助组件，包括胚胎花1（EMF 1），一种先前与PRC 1样复合物相关的转录抑制因子。综上所述，我们的数据表明，ALP 1抑制PcG沉默通过阻断核心PRC 2与促进其HMTase活性或其抑制转录的作用的辅助组分的相互作用。ALP 1是驯化转座酶获得作为PcG组分的新功能的第一个例子。经修饰的转座酶与PcG机器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宿主利用有益于基因活性的表观遗传调节的转座机器的特征的手段而出现。转座子是在其宿主基因组内增殖的寄生遗传元件。由于猖獗的转座通常是有害的，宿主已经进化出抑制转座子活性的方法。在植物中，这种基因组防御由Polycomb组（PcG）蛋白和/或DNA甲基化机制提供，其抑制转座酶基因的转录。我们确定了拟南芥ALP 1基因通过其作用，反对基因沉默介导的PcG基因。ALP 1是陆生植物中的一个古老基因，它是由一种驯化的转座酶进化而来的。出乎意料的是，我们发现ALP 1蛋白存在于PcG蛋白的保守复合物中，PcG蛋白通过甲基化包装DNA的组蛋白来抑制转录。ALP 1可能通过阻断其与刺激其活性的辅助蛋白的相互作用来抑制这种PcG复合物的活性。我们认为转座酶对PcG的抑制可能最初是作为转座子逃避宿主监视的一种手段而进化的，随后宿主可能利用这一点来调节PcG活性。我们的工作说明了转座子是如何成为朋友或敌人的，并提出了一个问题，即是否也会发现其他转座酶抑制其宿主的调节机制。
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. Transposons are parasitic genetic elements that proliferate within their hosts’ genomes. Because rampant transposition is usually deleterious, hosts have evolved ways to inhibit the activity of transposons. In plants, this genome defence is provided by the Polycomb group (PcG) proteins and/or the DNA methylation machinery, which repress the transcription of transposase genes. We identified the Arabidopsis ALP1 gene through its role in opposing gene silencing mediated by PcG genes. ALP1 is an ancient gene in land plants and has evolved from a domesticated transposase. Unexpectedly, we find that the ALP1 protein is present in a conserved complex of PcG proteins that inhibit transcription by methylating the histone proteins that package DNA. ALP1 likely inhibits the activity of this PcG complex by blocking its interaction with accessory proteins that stimulate its activity. We suggest that the inhibition of the PcG by a transposase may originally have evolved as a means for transposons to evade surveillance by their hosts, and that subsequently hosts may have exploited this as a means to regulate PcG activity. Our work illustrates how transposons can be friend or fiend, and raises the question of whether other transposases will also be found to inhibit their host’s regulatory machinery.