PfSET2 Is Involved in Genome Organization of Var Gene Family in Plasmodium falciparum.
PfSET2 Is Involved in Genome Organization of Var Gene Family in Plasmodium falciparum.
复制标题
PfSET2 参与恶性疟原虫 Var 基因家族的基因组组织
DOI：
10.1128/spectrum.03891-22
复制
发表时间：
2023-02-14
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
PfSET2在恶性疟原虫var基因沉默中起关键作用，但其潜在的分子机制尚不清楚。在这里，我们提供的证据表明，PfSET2对于维持异染色质区域的3D基因组组织以保持var基因处于转录抑制状态是必不可少的。这些发现有助于更好地理解恶性疟原虫高阶染色质结构的调控。恶性疟原虫的三维基因组结构是高度组织化的，在调节特定基因如毒力基因的协调表达模式中起着重要作用，这些基因参与了抗原变异和免疫逃逸。然而，控制寄生虫3D基因组的分子机制仍然难以捉摸。在这里，通过分析恶性疟原虫的基因组结构，我们发现了端粒和毒力基因座上具有较强染色质相互作用的高相互作用区(HIR)。具体地说，HIRS高度富含抑制性组蛋白标记(H3K36me3和H3K9me3)，形成转录抑制中心。控制H3K36me3水平的PfSET2缺失导致HIRS染色体内和染色体间相互作用显著减少。重要的是，这种染色质重组与HIRS表观遗传特征的动态变化和var基因的转录激活相协调。此外，基于染色质相互作用模式的不同var基因簇在PfSET2缺失后显示出不同的转录激活潜力。我们的研究结果揭示了表观遗传因子PfSET2调控恶性疟原虫异染色质三维结构调控var基因家族转录活性的基本机制。PfSET2的重要性已被报道在抑制恶性疟原虫var基因中发挥关键作用，但其潜在的分子机制尚不清楚。在这里，我们提供的证据表明，PfSET2对于维持异染色质区域的3D基因组组织以保持var基因处于转录抑制状态是必不可少的。这些发现有助于更好地理解恶性疟原虫高阶染色质结构的调控。
PfSET2 has been reported to play key role in silencing var genes in Plasmodium falciparum, while the underlying molecular mechanisms remain unclear. Here, we provide evidence that PfSET2 is essential to maintain 3D genome organization of heterochromatin region to keep var genes in transcription repressive state. These findings can contribute better understanding of the regulation of high-order chromatin structure in P. falciparum. ABSTRACT The three-dimensional (3D) genome structure of human malaria parasite Plasmodium falciparum is highly organized and plays important roles in regulating coordinated expression patterns of specific genes such as virulence genes which are involved in antigenic variation and immune escape. However, the molecular mechanisms that control 3D genome of the parasite remain elusive. Here, by analyzing genome organization of P. falciparum, we identify high-interacting regions (HIRs) with strong chromatin interactions at telomeres and virulence genes loci. Specifically, HIRs are highly enriched with repressive histone marks (H3K36me3 and H3K9me3) and form the transcriptional repressive center. Deletion of PfSET2, which controls H3K36me3 level, results in marked reduction of both intrachromosomal and interchromosomal interactions for HIRs. Importantly, such chromatin reorganization coordinates with dynamic changes in epigenetic feature in HIRs and transcriptional activation of var genes. Additionally, different cluster of var genes based on the pattern of chromatin interactions show distinct transcriptional activation potential after deletion of PfSET2. Our results uncover a fundamental mechanism that the epigenetic factor PfSET2 controls the 3D organization of heterochromatin to regulate the transcription activities of var genes family in P. falciparum. IMPORTANCE PfSET2 has been reported to play key role in silencing var genes in Plasmodium falciparum, while the underlying molecular mechanisms remain unclear. Here, we provide evidence that PfSET2 is essential to maintain 3D genome organization of heterochromatin region to keep var genes in transcription repressive state. These findings can contribute better understanding of the regulation of high-order chromatin structure in P. falciparum.
登录
查看更多内容
影响因子：
3.9
作者：
Karmodiya K;Pradhan SJ;Joshi B;Jangid R;Reddy PC;Galande S
通讯作者：
Galande S
影响因子：
9.6
作者：
Batugedara G;Lu XM;Bunnik EM;Le Roch KG
通讯作者：
Le Roch KG
DOI：
10.1038/nrmicro2145
发表时间：
2009-07
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Dowen JM;Fan ZP;Hnisz D;Ren G;Abraham BJ;Zhang LN;Weintraub AS;Schujiers J;Lee TI;Zhao K;Young RA
通讯作者：
Young RA
影响因子：
7.3
作者：
Batugedara G;Le Roch KG
通讯作者：
Le Roch KG