Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C).
Nat Genet, 2006/11;38(11):1348-54.
Simonis M[1], Klous P, Splinter E, Moshkin Y, Willemsen R, de Wit E, van Steensel B, de Laat W
Affiliations
PMID: 17033623
Impact factor: 41.307
Abstract
The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function. 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.
MeSH terms
Animals; Brain; Cell Nucleus; Chromatin; Chromatin Assembly and Disassembly; Chromosome Mapping; Chromosomes, Mammalian; DNA-Binding Proteins; Gene Expression Regulation; Globins; In Situ Hybridization, Fluorescence; Liver; Mice; Models, Biological; Nucleic Acid Conformation; Oligonucleotide Array Sequence Analysis
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