當(dāng)瘧疾寄生蟲“鐮刀形瘧原蟲”感染紅血球時(shí),，它逃避免疫檢測的辦法是,，一次只表達(dá)從抗原上來講截然不同的60個(gè)var基因中的一個(gè)，然后在感染過程中再改為表達(dá)一個(gè)新的基因,。在這項(xiàng)研究中,，Louis Miller及其同事發(fā)現(xiàn)，“組蛋白H3修飾賴氨酸36三甲基化”(H3K36me3) 存在于轉(zhuǎn)錄起始點(diǎn)上,，并沿被沉默的var基因的基因體（gene body）分布,。“使鐮刀形瘧原蟲變異體沉默的SET基因” (PfSETvs) 的剔除，導(dǎo)致所有60個(gè)var基因被同時(shí)轉(zhuǎn)錄,，其中每個(gè)基因編碼PfEMP1膜蛋白的一個(gè)不同版本,。因此PfSETvs在var基因沉默中起一個(gè)關(guān)鍵作用。另外,，這項(xiàng)研究中所生成的PfSETvs基因剔除寄生蟲因其能夠表達(dá)所有PfEMP1蛋白而具有用作一種抗瘧疾疫苗的潛力,，這樣應(yīng)能生成一個(gè)用來防止瘧疾的大范圍的抗體庫。（生物谷Bioon.com）
生物谷推薦英文摘要：
Nature doi:10.1038/nature12361
PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum
Lubin Jiang,Jianbing Mu,Qingfeng Zhang,Ting Ni,Prakash Srinivasan,Kempaiah Rayavara,Wenjing Yang,Louise Turner,Thomas Lavstsen,Thor G. Theander, Weiqun Peng,Guiying Wei,Qingqing Jing,Yoshiyuki Wakabayashi, Abhisheka Bansal,Yan Luo, José M. C. Ribeiro,Artur Scherf,L. Aravind,Jun Zhu,Keji Zhao & Louis H. Miller
The variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which is expressed on the surface of P. falciparum-infected red blood cells, is a critical virulence factor for malaria. Each parasite has 60 antigenically distinct var genes that each code for a different PfEMP1 protein. During infection the clonal parasite population expresses only one gene at a time before switching to the expression of a new variant antigen as an immune-evasion mechanism to avoid the host antibody response. The mechanism by which 59 of the 60 var genes are silenced remains largely unknown. Here we show that knocking out the P. falciparum variant-silencing SET gene (here termed PfSETvs), which encodes an orthologue of Drosophila melanogaster ASH1 and controls histone H3 lysine 36 trimethylation (H3K36me3) on var genes, results in the transcription of virtually all var genes in the single parasite nuclei and their expression as proteins on the surface of individual infected red blood cells. PfSETvs-dependent H3K36me3 is present along the entire gene body, including the transcription start site, to silence var genes. With low occupancy of PfSETvs at both the transcription start site of var genes and the intronic promoter, expression of var genes coincides with transcription of their corresponding antisense long noncoding RNA. These results uncover a previously unknown role of PfSETvs-dependent H3K36me3 in silencing var genes in P. falciparum that might provide a general mechanism by which orthologues of PfSETvs repress gene expression in other eukaryotes. PfSETvs knockout parasites expressing all PfEMP1 proteins may also be applied to the development of a malaria vaccine.
