Allele-specific chromatin immunoprecipitation studies show genetic influence on chromatin state in human genome.
Allele-specific chromatin immunoprecipitation studies show genetic influence on chromatin state in human genome.
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DOI：
10.1371/journal.pgen.0030081
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发表时间：
2007-05-18
期刊：
影响因子：
4.5
通讯作者：
Lee MP
中科院分区：
文献类型：
--
作者：
Kadota M;Yang HH;Hu N;Wang C;Hu Y;Taylor PR;Buetow KH;Lee MP
最近的几项研究表明，基因表达变异存在遗传影响，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。我们假设遗传继承也可能影响染色质状态的变异。为了验证这一假设，我们使用Affymetrix 10K单核苷酸多态性芯片，通过等位基因特异性染色质免疫沉淀（芯片上染色质免疫沉淀）分析，对来自两个人类多态性研究中心（CEPH）家庭的12个淋巴母细胞样细胞的染色质状态进行了分析。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12个淋巴母细胞样细胞进行了等位基因特异性芯片上染色质免疫沉淀分析。使用来自人类多态性研究中心家庭的多个细胞系使我们能够评估家系间染色质状态的变异。这些研究表明，染色质状态按家族聚类。我们的结果支持这样一种观点，即遗传继承可以决定染色质的表观遗传状态，正如之前在模式生物中所显示的那样。据我们所知，这是首次在人类中证明遗传可能是影响由组蛋白修饰介导的整体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。
人类健康和疾病是由遗传背景和环境暴露之间的相互作用决定的。正常发育和疾病都是由基因表达的表观遗传调控介导的。表观遗传调控导致基因表达的可遗传变化，这种变化与DNA序列变化无关。相反，它是由DNA的化学修饰（如DNA甲基化）或蛋白质修饰（如组蛋白乙酰化和甲基化）介导的。尽管在发育过程中的表观遗传继承方面已经了解很多，但对于遗传背景对诸如组蛋白修饰等表观遗传过程的影响知之甚少。在本报告中，作者在全基因组水平上研究了来自不同家庭的细胞中的五种组蛋白修饰。通过这些组蛋白修饰所测量的整体表观遗传状态，对于来自同一家庭的细胞显示出相似的模式。这项研究表明，遗传继承可能是影响人类中由组蛋白修饰介导的整体染色质状态的一个重要因素。这些观察结果说明了将遗传和表观遗传信息整合到人类健康和复杂疾病研究中的重要性。
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. Human health and disease are determined by an interaction between genetic background and environmental exposures. Both normal development and disease are mediated by epigenetic regulation of gene expression. The epigenetic regulation causes heritable changes in gene expression, which is not associated with DNA sequence changes. Instead, it is mediated by chemical modification of DNA such as DNA methylation or by protein modifications such as histone acetylation and methylation. Although much has been known about epigenetic inheritance during development, little is known about the influence of the genetic background on epigenetic processes such as histone modifications. In this report the authors studied five histone modifications on a genome-wide level in cells from different families. Global epigenetic states, as measured by these histone modifications, showed a similar pattern for cells derived from the same family. This study demonstrates that genetic inheritance may be an important factor influencing global chromatin states mediated by histone modifications in humans. These observations illustrate the importance of integrating genetic and epigenetic information into studies of human health and complex diseases.
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影响因子：
4.5
作者：
Tao, Heng;Cox, David R.;Frazer, Kelly A.
通讯作者：
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