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.

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Persistent URL dx.doi.org/10.1038/ncb2278, hdl.handle.net/1765/34364
Citation
Noordermeer, D., de Wit, E., Klous, P., van de Werken, H.J.G., Simonis, M., Lopez-Jones, M., … de Laat, W.L.. (2011). Variegated gene expression caused by cell-specific long-range DNA interactions. Nature Cell Biology, 13(8), 944–951. doi:10.1038/ncb2278