Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C).
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.
Simonis
Marieke
M
Department of Cell Biology and Genetics, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Klous
Petra
P
Splinter
Erik
E
Moshkin
Yuri
Y
Willemsen
Rob
R
de Wit
Elzo
E
van Steensel
Bas
B
de Laat
Wouter
W
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology; D002467:Cell Nucleus / Q000737:chemistry*; D002843:Chromatin / Q000737:chemistry*; D042002:Chromatin Assembly and Disassembly; D002874:Chromosome Mapping / Q000379:methods; D033481:Chromosomes, Mammalian / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D008954:Models, Biological; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*
D002843:Chromatin; D004268:DNA-Binding Proteins; C475578:Rad23a protein, mouse; D005914:Globins