Variegated gene expression caused by cell-specific long-range DNA interactions
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.
|Persistent URL||dx.doi.org/10.1038/ncb2278, hdl.handle.net/1765/34364|
Noordermeer, D, de Wit, E, Klous, P, van de Werken, H.J.G, Simonis, M.J, 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