对抗PRC——一种驯化的转座酶拮抗多梳蛋白介导的基因沉默,并且是多梳抑制复合物2的辅助成分。

Kicking against the PRCs - A Domesticated Transposase Antagonises Silencing Mediated by Polycomb Group Proteins and Is an Accessory Component of Polycomb Repressive Complex 2.

作者信息

Liang Shih Chieh, Hartwig Ben, Perera Pumi, Mora-García Santiago, de Leau Erica, Thornton Harry, de Lima Alves Flavia, Rappsilber Juri, Yang Suxin, James Geo Velikkakam, Schneeberger Korbinian, Finnegan E Jean, Turck Franziska, Goodrich Justin

机构信息

Institute of Molecular Plant Science, University of Edinburgh, Edinburgh, United Kingdom.

Department of Plant Developmental Biology, Max Planck Institute for Plant Breeding Research, Köln, Germany.

出版信息

PLoS Genet. 2015 Dec 7;11(12):e1005660. doi: 10.1371/journal.pgen.1005660. eCollection 2015 Dec.

Abstract

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.

摘要

多梳蛋白组(PcG)基因和三胸蛋白组(trxG)基因通过调控同源异型基因和其他控制细胞命运的基因的表达,在发育过程中发挥着关键作用。这两组基因都催化染色质修饰,尤其是组蛋白甲基化,从而导致影响基因活性的表观遗传变化。trxG通过激活PcG靶基因来拮抗PcG基因的功能,因此trxG突变体可抑制PcG突变体表型。我们之前鉴定出类异染色质蛋白1拮抗剂(ALP1)基因是拟南芥PcG基因类异染色质蛋白1(LHP1)突变体的遗传抑制因子。在此,我们表明ALP1与其他几个PcG和trxG组分存在遗传相互作用,并且它拮抗PcG沉默。转录谱分析表明,当PcG活性受损时,许多靶基因在幼苗中会被过度激活,而且在大多数情况下这需要ALP1。此外,当存在PcG活性时,ALP1是几个被PcG抑制的花同源异型基因完全激活所必需的。引人注目的是,ALP1并不编码已知的染色质蛋白,而是一种与PIF/先驱者类转座酶相关的蛋白。系统发育分析表明,ALP1在陆地植物中广泛保守,并且可能在被子植物进化过程中丧失了转座酶活性并获得了新功能。与此一致的是,免疫沉淀和质谱分析(IP-MS)表明,ALP1在体内与多梳抑制复合物2(PRC2)的核心组分相互作用,PRC2是一种广泛保守的PcG蛋白复合物,作为H3K27me3组蛋白甲基转移酶发挥作用。此外,在使用组蛋白甲基转移酶卷曲叶(CLF)进行的相互下拉实验中,我们不仅鉴定出了ALP1和PRC2核心组分,还鉴定出了植物特异性辅助组分,包括胚胎花1(EMF1),一种先前与类PRC1复合物相关的转录抑制因子。综合我们的数据表明,ALP1通过阻断核心PRC2与促进其HMTase活性或其在抑制转录中作用的辅助组分之间的相互作用来抑制PcG沉默。ALP1是驯化的转座酶获得作为PcG组分的新功能的首个例子。修饰后的转座酶与PcG机制的拮抗相互作用是新颖的,可能是同源转座子逃避宿主监测的一种方式,或者是宿主利用转座机制的特征来促进基因活性的表观遗传调控所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8c7/4671723/f34ad3d72858/pgen.1005660.g001.jpg

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