Freaney Jonathan E, Zhang Quanwei, Yigit Erbay, Kim Rebecca, Widom Jonathan, Wang Ji-Ping, Horvath Curt M
1 Department of Molecular Biosciences, Northwestern University , Evanston, Illinois.
J Interferon Cytokine Res. 2014 Sep;34(9):676-85. doi: 10.1089/jir.2013.0118. Epub 2014 Mar 27.
Genome-wide investigations have dramatically increased our understanding of nucleosome positioning and the role of chromatin in gene regulation, yet some genomic regions have been poorly represented in human nucleosome maps. One such region is represented by human chromosome 9p21-22, which contains the type I interferon gene cluster that includes 16 interferon alpha genes and the single interferon beta, interferon epsilon, and interferon omega genes. A high-density nucleosome mapping strategy was used to generate locus-wide maps of the nucleosome organization of this biomedically important locus at a steady state and during a time course of infection with Sendai virus, an inducer of interferon gene expression. Detailed statistical and computational analysis illustrates that nucleosomes in this locus exhibit preferences for particular dinucleotide and oligomer DNA sequence motifs in vivo, which are similar to those reported for lower eukaryotic nucleosome-DNA interactions. These data were used to visualize the region's chromatin architecture and reveal features that are common to the organization of all the type I interferon genes, indicating a common nucleosome-mediated gene regulatory paradigm. Additionally, this study clarifies aspects of the dynamic changes that occur with the nucleosome occupying the transcriptional start site of the interferon beta gene after virus infection.
全基因组研究极大地增进了我们对核小体定位以及染色质在基因调控中作用的理解,然而在人类核小体图谱中,一些基因组区域的代表性不足。人类9号染色体p21 - 22区域就是这样一个例子,该区域包含I型干扰素基因簇,其中有16个干扰素α基因以及单个的干扰素β、干扰素ε和干扰素ω基因。采用高密度核小体图谱绘制策略,在稳定状态下以及在感染仙台病毒(一种干扰素基因表达诱导剂)的时间进程中,生成了这个具有重要生物医学意义位点的全基因座核小体组织图谱。详细的统计和计算分析表明,该位点的核小体在体内对特定的二核苷酸和寡聚体DNA序列基序表现出偏好,这与报道的低等真核生物核小体 - DNA相互作用类似。这些数据用于可视化该区域的染色质结构,并揭示所有I型干扰素基因组织共有的特征,表明存在一种共同的核小体介导的基因调控模式。此外,这项研究阐明了病毒感染后占据干扰素β基因转录起始位点的核小体发生动态变化的一些方面。