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

117 Scopus citations

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

ASJC Scopus subject areas

  • Cell Biology

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    Noordermeer, D., De Wit, E., Klous, P., Van De Werken, H., Simonis, M., Lopez-Jones, M., Eussen, B., De Klein, A., Singer, R. H., & 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