生物谷報道：大部分的成年人都曾經(jīng)受到單純皰疹病毒第一型（HSV-1）的感染，患者受到感染后,，病毒通常會留存于體內(nèi),，躲避在患者的神經(jīng)細(xì)胞附近，以逃避免疫系統(tǒng)的防御機(jī)制,。
為了逃避身體免疫系統(tǒng)的偵測,，潛藏的病毒會使負(fù)責(zé)病毒復(fù)制的基因靜默。在這個休眠狀態(tài)中,，只有病毒染色體的一個微小片段- 一種稱為Latency-Associated Transcript (LAT)的單一基因仍然活化,。
科學(xué)家長久以來，一直困惑著這一小塊染色體區(qū)域維持活化的原因?，F(xiàn)在,，Wistar研究所的科學(xué)家發(fā)現(xiàn)了一個保持HSV-1只被單一基因活化的分子機(jī)制。研究員辨認(rèn)了一個隔離者DNA,，大約只有800個堿基對,，可作為病毒染色體活化和非活化區(qū)域間的物理屏障。
因此皰疹病毒可以讓這一小塊染色體區(qū)域不會靜默,，允許受感染的細(xì)胞生存,。這項研究結(jié)果發(fā)表于5月號的Journal of Virology中,。 （姜欣慧譯）
(資料來源 : Bio.com)
英文原文鏈接：
原始出處:
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.
