Nature Genetics
- 38, 1348 - 1354 (2006)
Published online: 8 October 2006; | doi:10.1038/ng1896
Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture–on-chip (4C)Marieke Simonis1, Petra Klous1, Erik Splinter1, Yuri Moshkin2, Rob Willemsen3, Elzo de Wit4, Bas van Steensel4 & Wouter de Laat11
Department of Cell Biology and Genetics, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands. 2
Department of Biochemistry, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands. 3
Department of Clinical Genetics, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands. 4
Division of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Correspondence should be addressed to Wouter de Laat w.delaat@erasmusmc.nl The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function1,
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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  -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.
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