Variegated gene expression caused by cell-specific long-range DNA interactions
Author: ["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"]
Publication: Nature Cell Biology
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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. How regulatory elements spatially interact with their target DNA sequences is unclear. The β-globin locus control region (LCR) is found to take part in interchromosomal interactions with a few genes controlled by shared transcription factors, and to transcriptionally upregulate β-globin mRNA in a subset of cells.
Cite this article
Noordermeer, D., de Wit, E., Klous, P. et al. Variegated gene expression caused by cell-specific long-range DNA interactions. Nat Cell Biol 13, 944–951 (2011). https://doi.org/10.1038/ncb2278
