J. Virol.：隔离者DNA有助于使休眠的疱疹病毒基因静默
生物谷报道：大部分的成年人都曾经受到单纯疱疹病毒第一型（HSV-1）的感染，患者受到感染后，病毒通常会留存于体内，躲避在患者的神经细胞附近，以逃避免疫系统的防御机制。
为了逃避身体免疫系统的侦测，潜藏的病毒会使负责病毒复制的基因静默。在这个休眠状态中，只有病毒染色体的一个微小片段- 一种称为Latency-Associated Transcript (LAT)的单一基因仍然活化。
科学家长久以来，一直困惑着这一小块染色体区域维持活化的原因。现在，Wistar研究所的科学家发现了一个保持HSV-1只被单一基因活化的分子机制。研究员辨认了一个隔离者DNA，大约只有800个碱基对，可作为病毒染色体活化和非活化区域间的物理屏障。
因此疱疹病毒可以让这一小块染色体区域不会静默，允许受感染的细胞生存。这项研究结果发表于5月号的Journal of Virology中。 （姜欣慧译）
(资料来源 : Bio.com)
英文原文链接：
原始出处:
Journal of Virology, May 2007, p. 5192-5201, Vol. 81, No. 10
CTCF-Dependent Chromatin Boundary Element between the Latency-Associated Transcript and ICP0 Promoters in the Herpes Simplex Virus Type 1 Genome
Qi Chen,
Lan Lin, Sheryl Smith, Jing Huang, Shelley L. Berger, and Jumin Zhou*
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104
Received 6 November 2006/ Accepted 24 January 2007
Abstract
Cells latently infected with herpes simplex virus (HSV) contain nucleosomal DNA similar to that of host cell chromatin. Recent studies have demonstrated that histones in the latency-associated transcript (LAT) promoter and intron regions contain histone modifications permissive for transcription. However, those histones associated with the lytic-specific ICP0 gene, which lies only 5 kb away, contain modifications typical of silenced chromatin. How this active chromatin is kept separate from the repressed chromatin in the nearby ICP0 region remains crucial to the understanding of the HSV lytic cycle. In this study, we show that the LAT intron region contains an insulator. Specifically, we show that an 800-bp region from the LAT intron can block enhancers in both tissue culture cells and Drosophila melanogaster embryos. Importantly, the 800-bp HSV insulator protects a LAT transgene from positional effects in Drosophila eye tissue. The 800-bp region contains nine copies of 16-bp repeats. In vitro electrophoretic mobility shift assay revealed that CTCF interacts with the CTCCC sequence within the repeats. In vivo chromatin immunoprecipitation assay demonstrated that CTCF interacts with these repeats in latently infected trigeminal ganglion neurons. The deletion of these repeats impaired insulator activity in human K562 cells and Drosophila embryos. Finally, double-spaced RNA knockdown of CTCF disrupts enhancer-blocking activity of the LAT insulator in transfected Drosophila S3 cells. These results strongly support the hypothesis that the 800-bp DNA in the LAT intron region works as a chromatin boundary during latency to separate active chromatin associated with the LAT promoter region from repressed chromatin in the ICP0 gene.
相关报道:
- 众说风云 (已有2条评论)
