Variegated gene expression caused by cell-specific long-range DNA interactions

Daan Noordermeer, Elzo De Wit, Petra Klous, Harmen Van De Werken, Marieke Simonis, Melissa Lopez-Jones, Bert Eussen, Annelies De Klein, Robert H. Singer, Wouter De Laat

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Mammalian genomes contain numerous regulatory DNA sites with unknown target genes. We used mice with an extra β-globin locus control region (LCR) to investigate how a regulator searches the genome for target genes. We find that the LCR samples a restricted nuclear subvolume, wherein it preferentially contacts genes controlled by shared transcription factors. No contacted gene is detectably upregulated except for endogenous β-globin genes located on another chromosome. This demonstrates genetically that mammalian trans activation is possible, but suggests that it will be rare. Trans activation occurs not pan-cellularly, but in jackpot cells enriched for the interchromosomal interaction. Therefore, cell-specific long-range DNA contacts can cause variegated expression.

Original languageEnglish (US)
Pages (from-to)944-951
Number of pages8
JournalNature Cell Biology
Volume13
Issue number8
DOIs
StatePublished - Aug 2011

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Gene Expression
Locus Control Region
DNA
Globins
Genes
Genome
Transcription Factors
Chromosomes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Noordermeer, D., De Wit, E., Klous, P., Van De Werken, H., Simonis, M., Lopez-Jones, M., ... De Laat, W. (2011). Variegated gene expression caused by cell-specific long-range DNA interactions. Nature Cell Biology, 13(8), 944-951. https://doi.org/10.1038/ncb2278

Variegated gene expression caused by cell-specific long-range DNA interactions. / Noordermeer, Daan; De Wit, Elzo; Klous, Petra; Van De Werken, Harmen; Simonis, Marieke; Lopez-Jones, Melissa; Eussen, Bert; De Klein, Annelies; Singer, Robert H.; De Laat, Wouter.

In: Nature Cell Biology, Vol. 13, No. 8, 08.2011, p. 944-951.

Research output: Contribution to journalArticle

Noordermeer, D, De Wit, E, Klous, P, Van De Werken, H, Simonis, M, Lopez-Jones, M, Eussen, B, De Klein, A, Singer, RH & De Laat, W 2011, 'Variegated gene expression caused by cell-specific long-range DNA interactions', Nature Cell Biology, vol. 13, no. 8, pp. 944-951. https://doi.org/10.1038/ncb2278
Noordermeer D, De Wit E, Klous P, Van De Werken H, Simonis M, Lopez-Jones M et al. Variegated gene expression caused by cell-specific long-range DNA interactions. Nature Cell Biology. 2011 Aug;13(8):944-951. https://doi.org/10.1038/ncb2278
Noordermeer, Daan ; De Wit, Elzo ; Klous, Petra ; Van De Werken, Harmen ; Simonis, Marieke ; Lopez-Jones, Melissa ; Eussen, Bert ; De Klein, Annelies ; Singer, Robert H. ; De Laat, Wouter. / Variegated gene expression caused by cell-specific long-range DNA interactions. In: Nature Cell Biology. 2011 ; Vol. 13, No. 8. pp. 944-951.
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