尽管在布氏锥虫中仅单等位基因表达，但转录仍在沉默的表面糖蛋白表达位点起始。
Transcription is initiated on silent variant surface glycoprotein expression sites despite monoallelic expression in Trypanosoma brucei.
机构信息
Laboratory of Molecular Parasitology, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, 6041 Gosselies, Belgium.
Laboratory of Molecular Parasitology, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, 6041 Gosselies, Belgium
出版信息
Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):8943-8. doi: 10.1073/pnas.1404873111. Epub 2014 Jun 2.
Abstract
African trypanosomes survive the immune defense of their hosts by regularly changing their antigenic coat made of variant surface glycoprotein (VSG). The Trypanosoma brucei genome contains more than 1,000 VSG genes. To be expressed, a given VSG gene must be located in one of 15 telomeric regions termed "VSG expression sites" (ESs), each of which contains a polycistronic transcription unit that includes ES-associated genes. Only one ES is fully active at a time, so only one VSG gene is transcribed per cell. Although this monoallelic expression is controlled at the transcriptional level, the precise molecular mechanism for this control is not understood. Here we report that in single cells transcription is initiated on several ESs simultaneously, indicating that the monoallelic control is not determined only at transcription initiation, but also at further control steps such as transcription elongation or RNA processing.
摘要
非洲锥虫通过定期改变其由变异表面糖蛋白 (VSG) 组成的抗原外壳来逃避宿主的免疫防御。布氏锥虫基因组包含超过 1000 个 VSG 基因。为了表达，给定的 VSG 基因必须位于 15 个端粒区域之一中，这些区域称为“VSG 表达位点”（ES），每个 ES 都包含一个多顺反子转录单元，其中包括 ES 相关基因。一次只有一个 ES 完全活跃，因此每个细胞仅转录一个 VSG 基因。尽管这种单等位基因表达是在转录水平上控制的，但这种控制的确切分子机制尚不清楚。在这里，我们报告说在单个细胞中，几个 ES 同时启动转录，这表明单等位基因控制不仅在转录起始时确定，而且在转录延伸或 RNA 处理等进一步的控制步骤中确定。
相似文献
1
Transcription is initiated on silent variant surface glycoprotein expression sites despite monoallelic expression in Trypanosoma brucei.尽管在布氏锥虫中仅单等位基因表达，但转录仍在沉默的表面糖蛋白表达位点起始。
Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):8943-8. doi: 10.1073/pnas.1404873111. Epub 2014 Jun 2.
2
Dynamic colocalization of 2 simultaneously active expression sites within a single expression-site body in .在. 中，单个表达体中 2 个同时活跃的表达位点的动态共定位。
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16561-16570. doi: 10.1073/pnas.1905552116. Epub 2019 Jul 29.
3
Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes.肌醇磷酸途径控制锥虫端粒表达位点的转录。
Proc Natl Acad Sci U S A. 2015 May 26;112(21):E2803-12. doi: 10.1073/pnas.1501206112. Epub 2015 May 11.
4
The VSG expression sites of Trypanosoma brucei: multipurpose tools for the adaptation of the parasite to mammalian hosts.布氏锥虫的VSG表达位点：寄生虫适应哺乳动物宿主的多功能工具
Mol Biochem Parasitol. 2001 Apr 25;114(1):1-16. doi: 10.1016/s0166-6851(01)00242-0.
5
Loss of the mono-allelic control of the VSG expression sites during the development of Trypanosoma brucei in the bloodstream.在布氏锥虫于血液中发育期间，VSG 表达位点的单等位基因控制丧失。
Mol Microbiol. 2004 Mar;51(6):1577-88. doi: 10.1111/j.1365-2958.2003.03937.x.
6
Leaky transcription of variant surface glycoprotein gene expression sites in bloodstream african trypanosomes.非洲锥虫血流期变体表面糖蛋白基因表达位点的渗漏转录
J Biol Chem. 1999 Jun 11;274(24):16884-93. doi: 10.1074/jbc.274.24.16884.
7
Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei.表达位点衰减在机制上连接了布氏锥虫的抗原变异与发育。
Elife. 2014 May 20;3:e02324. doi: 10.7554/eLife.02324.
8
Monoallelic expression and epigenetic inheritance sustained by a Trypanosoma brucei variant surface glycoprotein exclusion complex.单等位基因表达和表观遗传遗传由布氏锥虫变体表面糖蛋白排除复合物维持。
Nat Commun. 2019 Jul 9;10(1):3023. doi: 10.1038/s41467-019-10823-8.
9
Telomere exchange can be an important mechanism of variant surface glycoprotein gene switching in Trypanosoma brucei.端粒交换可能是布氏锥虫变异表面糖蛋白基因转换的重要机制。
Mol Biochem Parasitol. 1996 Sep;80(1):65-75. doi: 10.1016/0166-6851(96)02669-2.
10
The anatomy and transcription of a monocistronic expression site for a metacyclic variant surface glycoprotein gene in Trypanosoma brucei.布氏锥虫中环体变异表面糖蛋白基因单顺反子表达位点的结构与转录
J Biol Chem. 1999 Jun 11;274(24):16876-83. doi: 10.1074/jbc.274.24.16876.
引用本文的文献
1
Precision-edited histone tails disrupt polycistronic gene expression controls in trypanosomes.精确编辑的组蛋白尾巴破坏了锥虫中的多顺反子基因表达控制。
Nat Commun. 2025 Jul 4;16(1):6194. doi: 10.1038/s41467-025-61480-z.
2
TelAP2 links TelAP1 to the telomere complex in Trypanosoma brucei.在布氏锥虫中，TelAP2将TelAP1与端粒复合体相连。
Sci Rep. 2024 Dec 16;14(1):30493. doi: 10.1038/s41598-024-81972-0.
3
Protein phosphatase PP1 regulation of RNA polymerase II transcription termination and allelic exclusion of VSG genes in trypanosomes.蛋白磷酸酶 PP1 调控 RNA 聚合酶 II 转录终止和锥虫 VSG 基因的等位基因排斥。
Nucleic Acids Res. 2024 Jul 8;52(12):6866-6885. doi: 10.1093/nar/gkae392.
4
Unwrap RAP1's Mystery at Kinetoplastid Telomeres.揭开动基体端粒中 RAP1 的神秘面纱。
Biomolecules. 2024 Jan 4;14(1):67. doi: 10.3390/biom14010067.
5
The RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression.在 T. brucei RAP1 中，RRM 介导的 RNA 结合活性对于 VSG 单等位基因表达是必需的。
Nat Commun. 2023 Mar 22;14(1):1576. doi: 10.1038/s41467-023-37307-0.
6
Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei.阶段特异性转录激活因子 ESB1 调控布氏锥虫单等位基因抗原的表达。
Nat Microbiol. 2022 Aug;7(8):1280-1290. doi: 10.1038/s41564-022-01175-z. Epub 2022 Jul 25.
7
Pedal to the Metal: Nuclear Splicing Bodies Turbo-Charge VSG mRNA Production in African Trypanosomes.全力以赴：核剪接体加速非洲锥虫中VSG mRNA的产生
Front Cell Dev Biol. 2022 Apr 20;10:876701. doi: 10.3389/fcell.2022.876701. eCollection 2022.
8
VEX1 Influences mVSG Expression During the Transition to Mammalian Infectivity in .VEX1在向哺乳动物传染性转变过程中影响变异表面糖蛋白（mVSG）的表达 。 （你提供的原文句子不完整，这里是按照合理补充后的内容进行翻译，原句中“in”后面缺少具体内容）
Front Cell Dev Biol. 2022 Apr 5;10:851475. doi: 10.3389/fcell.2022.851475. eCollection 2022.
9
Shared Mechanisms for Mutually Exclusive Expression and Antigenic Variation by Protozoan Parasites.原生动物寄生虫互斥表达和抗原变异的共同机制
Front Cell Dev Biol. 2022 Mar 8;10:852239. doi: 10.3389/fcell.2022.852239. eCollection 2022.
10
May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression.愿幸运常伴你左右：使细胞表面分子表达多样化的非确定性机制
Front Cell Dev Biol. 2022 Jan 11;9:720798. doi: 10.3389/fcell.2021.720798. eCollection 2021.
本文引用的文献
1
Promoter occupancy of the basal class I transcription factor A differs strongly between active and silent VSG expression sites in Trypanosoma brucei.在布氏锥虫中，基本类 I 转录因子 A 的启动子占据与活性和沉默 VSG 表达位点有很大差异。
Nucleic Acids Res. 2014 Mar;42(5):3164-76. doi: 10.1093/nar/gkt1301. Epub 2013 Dec 17.
2
Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control.非洲锥虫的抗原变异：染色体和核环境在 VSG 表达调控中的重要性。
Cell Microbiol. 2013 Dec;15(12):1984-93. doi: 10.1111/cmi.12215. Epub 2013 Oct 10.
3
MCM-BP is required for repression of life-cycle specific genes transcribed by RNA polymerase I in the mammalian infectious form of Trypanosoma brucei.MCM-BP 对于 RNA 聚合酶 I 转录的生命周期特异性基因在哺乳动物感染型布氏锥虫中的抑制是必需的。
PLoS One. 2013;8(2):e57001. doi: 10.1371/journal.pone.0057001. Epub 2013 Feb 25.
4
TDP1 is an HMG chromatin protein facilitating RNA polymerase I transcription in African trypanosomes.TDP1 是一种 HMG 染色质蛋白，可促进非洲锥虫中的 RNA 聚合酶 I 转录。
Nucleic Acids Res. 2013 Mar 1;41(5):2981-92. doi: 10.1093/nar/gks1469. Epub 2013 Jan 29.
5
Trypanosoma brucei Orc1 is essential for nuclear DNA replication and affects both VSG silencing and VSG switching.布氏锥虫 Orc1 对于核 DNA 复制是必需的，并且影响 VSG 沉默和 VSG 切换。
Mol Microbiol. 2013 Jan;87(1):196-210. doi: 10.1111/mmi.12093. Epub 2012 Dec 10.
6
Histone H1 plays a role in heterochromatin formation and VSG expression site silencing in Trypanosoma brucei.组蛋白 H1 在布氏锥虫异染色质形成和 VSG 表达位点沉默中起作用。
PLoS Pathog. 2012;8(11):e1003010. doi: 10.1371/journal.ppat.1003010. Epub 2012 Nov 1.
7
Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b in Trypanosoma brucei.细胞周期调控的组蛋白和组蛋白伴侣 ASF1A 和 CAF-1b 对布鲁氏锥虫 VSG 表达沉默的调控。
Nucleic Acids Res. 2012 Nov 1;40(20):10150-60. doi: 10.1093/nar/gks813. Epub 2012 Aug 31.
8
NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions.NUP-1 是一种大型卷曲螺旋核骨架蛋白，在原生动物中具有类似于层粘连蛋白的功能。
PLoS Biol. 2012;10(3):e1001287. doi: 10.1371/journal.pbio.1001287. Epub 2012 Mar 27.
9
Identification of ORC1/CDC6-interacting factors in Trypanosoma brucei reveals critical features of origin recognition complex architecture.鉴定布氏锥虫 ORC1/CDC6 相互作用因子揭示了起始识别复合物结构的关键特征。
PLoS One. 2012;7(3):e32674. doi: 10.1371/journal.pone.0032674. Epub 2012 Mar 8.
10
The WHO policy package to combat antimicrobial resistance.世界卫生组织应对抗菌药物耐药性的一揽子政策。
Bull World Health Organ. 2011 May 1;89(5):390-2. doi: 10.2471/BLT.11.088435.
Zotero 插件