Nucleosome maps of the human cytomegalovirus genome reveal a temporal switch in chromatin organization linked to a major IE protein.
Nucleosome maps of the human cytomegalovirus genome reveal a temporal switch in chromatin organization linked to a major IE protein.
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人类巨细胞病毒基因组的核小体图谱揭示了与主要 IE 蛋白相关的染色质组织的时间转换。
DOI：
10.1073/pnas.1305548110
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发表时间：
2013
影响因子：
11.1
通讯作者：
Nevels,Michael
中科院分区：
文献类型：
--
作者：
Zalckvar,Einat;Paulus,Christina;Tillo,Desiree;Asbach-Nitzsche,Alexandra;Lubling,Yaniv;Winterling,Carla;Strieder,Nicholas;Mücke,Katrin;Goodrum,Felicia;Segal,Eran;Nevels,Michael
人类巨细胞病毒(HCMV)在我们大多数人中建立了终身感染，导致人类胚胎的发育缺陷和免疫受损个体的危及生命的疾病。在生产性感染期间，病毒230,000个碱基对的dsDNA基因组广泛表达，并在时间上级联。巨细胞病毒基因组被包裹时不携带组蛋白，但被认为在释放到宿主细胞核后形成核小体。在这里，我们提出了人类巨细胞病毒全基因组核小体占有率和新生转录图谱。我们表明，核小体以一种非随机和高度可预测的方式占据核病毒DNA。在感染的早期，核小体主要根据其固有的DNA序列偏好与HCMV基因组结合，表明初始核小体的形成是在病毒中遗传编码的。然而，随着感染进展到后期，核小体广泛地重新分布，以建立主要由非遗传因素决定的模式。我们认为这些因素包括编码在HCMV主要即刻早期(IE)基因座的病毒基因表达的关键调控因素。事实上，与WT基因组相比，IE1表达缺陷的突变病毒基因组表现出全球核小体负载增加和核小体动态减少。IE1缺陷病毒和WT病毒在时间上的核小体占有率差异与病毒新生模式和总转录积累的变化成反比。这些结果提供了一个跨越人类主要病原体基因组的空间和时间核小体组织的框架，并表明HCMV主要的IE蛋白控制整个病毒染色质的结构和功能。
Human CMV (hCMV) establishes lifelong infections in most of us, causing developmental defects in human embryos and life-threatening disease in immunocompromised individuals. During productive infection, the viral >230,000-bp dsDNA genome is expressed widely and in a temporal cascade. The hCMV genome does not carry histones when encapsidated but has been proposed to form nucleosomes after release into the host cell nucleus. Here, we present hCMV genome-wide nucleosome occupancy and nascent transcript maps during infection of permissive human primary cells. We show that nucleosomes occupy nuclear viral DNA in a nonrandom and highly predictable fashion. At early times of infection, nucleosomes associate with the hCMV genome largely according to their intrinsic DNA sequence preferences, indicating that initial nucleosome formation is genetically encoded in the virus. However, as infection proceeds to the late phase, nucleosomes redistribute extensively to establish patterns mostly determined by nongenetic factors. We propose that these factors include key regulators of viral gene expression encoded at the hCMV major immediate-early (IE) locus. Indeed, mutant virus genomes deficient for IE1 expression exhibit globally increased nucleosome loads and reduced nucleosome dynamics compared with WT genomes. The temporal nucleosome occupancy differences between IE1-deficient and WT viruses correlate inversely with changes in the pattern of viral nascent and total transcript accumulation. These results provide a framework of spatial and temporal nucleosome organization across the genome of a major human pathogen and suggest that an hCMV major IE protein governs overall viral chromatin structure and function.
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影响因子：
3.2
作者：
MADRI, JA;PRATT, BM
通讯作者：
PRATT, BM
DOI：
--
发表时间：
1986
期刊：
The American journal of pathology
影响因子：
--
作者：
D. Ingber;J. Madri;J. Jamieson
通讯作者：
D. Ingber;J. Madri;J. Jamieson
影响因子：
3.7
作者：
LWEBUGAMUKASA, JS;INGBAR, DH;MADRI, JA
通讯作者：
MADRI, JA
DOI：
10.1073/pnas.78.6.3901
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
INGBER, DE;MADRI, JA;JAMIESON, JD
通讯作者：
JAMIESON, JD
DOI：
--
发表时间：
1987
期刊：
The American journal of pathology
影响因子：
--
作者：
Keller,R;Silbert,JE;Furthmayr,H;Madri,JA
通讯作者：
Madri,JA