Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture–on-chip (4C)
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.
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In 4C experiments, the LCR was found to interact with multiple highly transcribed genes in the corresponding active cell type (foetal liver) but with different, transcriptionally silent genes in an inactive cell type (brain tissue).
“In 4C experiments, the LCR was found to interact with multiple highly transcribed genes in the corresponding active cell type (foetal liver) but with different, transcriptionally silent genes in an inactive cell type (brain tissue) [269].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [269]
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- Authors
- Simonis, M., Klous, P., Splinter, E., Moshkin, Y., Willemsen, R., de Wit, E., van Steensel, B., & de Laat, W.
- Affiliations
- Erasmus MC (NL)
- Venue
- Nature Genetics
- Published
- 2006-10-08
- Volume
- 38
- Issue
- 11
- Pages
- 1348-1354
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1991149014
- Cited by
- 1,386
- References
- 0
- Citations by year
- 2026: 26 · 2025: 47 · 2024: 39 · 2023: 48 · 2022: 65 · 2021: 81 · 2020: 119 · 2019: 91 · 2018: 88 · 2017: 59 · 2016: 77 · 2015: 78 · 2014: 75 · 2013: 85 · 2012: 86
- FWCI
- 20.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- nuclear organization, chromatin organization, active chromatin, inactive chromatin, beta-globin locus, fetal liver, fetal brain, chromosome 7, chromosome 8, tissue-specific gene expression, chromatin folding
- MeSH terms
- Animals, Brain, Cell Nucleus, Chromatin, Chromosome Mapping, DNA-Binding Proteins, Gene Expression Regulation, Globins, Liver, Models, Biological, Nucleic Acid Conformation, In Situ Hybridization, Fluorescence, Oligonucleotide Array Sequence Analysis, Chromosomes, Mammalian, Chromatin Assembly and Disassembly, Mice
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