Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C)
Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C)
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DOI：
10.1038/ng1896
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发表时间：
2006-11-01
期刊：
影响因子：
30.8
通讯作者：
de Laat, Wouter
中科院分区：
文献类型：
--
作者：
Simonis, Marieke;Klous, Petra;de Laat, Wouter
细胞核中DNA的空间组织是基因组功能的一个新兴关键因素（1-12）。我们开发了4C技术（芯片上的染色体构象捕获（3C）），它允许无偏倚地在全基因组范围内搜索与核空间中给定位点接触的DNA位点。我们在这里证明，活性和非活性基因参与许多远程染色体内相互作用，也可以形成染色体间接触。胎儿肝脏中活跃的β -珠蛋白位点优先接触7号染色体上转录的，但不一定是组织特异性的位点，而胎儿大脑中不活跃的位点接触不同的转录沉默位点。8号染色体上一个基因密集区域的管家基因主要与其他活性基因簇形成远程接触，包括顺式和反式，并且许多这些染色体内和染色体间的相互作用在分析的组织之间是保守的。我们的数据表明染色体折叠成活性染色质区域和非活性染色质区域，并建立了4C技术作为研究核结构的有力工具。
The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function(1-12). We developed 4C technology (chromosome conformation capture (3C)-on-chip), which allows for an unbiased genome-wide search for DNA loci that contact a given locus in the nuclear space. We demonstrate here that active and inactive genes are engaged in many long-range intrachromosomal interactions and can also form interchromosomal contacts. The active beta-globin locus in fetal liver preferentially contacts transcribed, but not necessarily tissue-specific, loci elsewhere on chromosome 7, whereas the inactive locus in fetal brain contacts different transcriptionally silent loci. A housekeeping gene in a gene-dense region on chromosome 8 forms long-range contacts predominantly with other active gene clusters, both in cis and in trans, and many of these intra- and interchromosomal interactions are conserved between the tissues analyzed. Our data demonstrate that chromosomes fold into areas of active chromatin and areas of inactive chromatin and establish 4C technology as a powerful tool to study nuclear architecture.