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

D (Daan) Noordermeer, E (Emmie) de Wit, PM Klous, Harmen van de Werken, Marcel Simonis, M Lopez-Jones, B Eussen, Annelies de Klein, RH Singer, WL (Wouter) de Laat

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126 Citations (Scopus)

Abstract

Mammalian genomes contain numerous regulatory DNA sites with unknown target genes. We used mice with an extra beta-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 beta-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 languageUndefined/Unknown
Pages (from-to)944-U161
JournalNature Cell Biology
Volume13
Issue number8
DOIs
Publication statusPublished - 2011

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