Kadota Mitsutaka, Yang Howard H, Hu Nan, Wang Chaoyu, Hu Ying, Taylor Philip R, Buetow Kenneth H, Lee Maxwell P
Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS Genet. 2007 May 18;3(5):e81. doi: 10.1371/journal.pgen.0030081.
Several recent studies have shown a genetic influence on gene expression variation, including variation between the two chromosomes within an individual and variation between individuals at the population level. We hypothesized that genetic inheritance may also affect variation in chromatin states. To test this hypothesis, we analyzed chromatin states in 12 lymphoblastoid cells derived from two Centre d'Etude du Polymorphisme Humain families using an allele-specific chromatin immunoprecipitation (ChIP-on-chip) assay with Affymetrix 10K SNP chip. We performed the allele-specific ChIP-on-chip assays for the 12 lymphoblastoid cells using antibodies targeting at RNA polymerase II and five post-translation modified forms of the histone H3 protein. The use of multiple cell lines from the Centre d'Etude du Polymorphisme Humain families allowed us to evaluate variation of chromatin states across pedigrees. These studies demonstrated that chromatin state clustered by family. Our results support the idea that genetic inheritance can determine the epigenetic state of the chromatin as shown previously in model organisms. To our knowledge, this is the first demonstration in humans that genetics may be an important factor that influences global chromatin state mediated by histone modification, the hallmark of the epigenetic phenomena.
最近的几项研究表明基因对基因表达变异存在影响，包括个体内两条染色体之间的变异以及群体水平上个体之间的变异。我们推测基因遗传可能也会影响染色质状态的变异。为了验证这一假设，我们使用Affymetrix 10K SNP芯片通过等位基因特异性染色质免疫沉淀（芯片上的染色质免疫沉淀，ChIP-on-chip）分析了来自两个人类多态性研究中心（Centre d'Etude du Polymorphisme Humain）家族的12个淋巴母细胞的染色质状态。我们使用针对RNA聚合酶II和组蛋白H3蛋白的五种翻译后修饰形式的抗体，对这12个淋巴母细胞进行了等位基因特异性芯片上的染色质免疫沉淀分析。使用来自人类多态性研究中心家族的多个细胞系使我们能够评估不同家系中染色质状态的变异。这些研究表明染色质状态按家族聚类。我们的结果支持了如下观点：正如之前在模式生物中所显示的那样，基因遗传可以决定染色质的表观遗传状态。据我们所知，这是在人类中的首次证明，即遗传学可能是影响由组蛋白修饰介导的全局染色质状态的一个重要因素，而组蛋白修饰是表观遗传现象的标志。
