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

First Author  Noordermeer D Year  2011
Journal  Nat Cell Biol Volume  13
Issue  8 Pages  944-51
PubMed ID  21706023 Mgi Jnum  J:264340
Mgi Id  MGI:6195131 Doi  10.1038/ncb2278
Citation  Noordermeer D, et al. (2011) Variegated gene expression caused by cell-specific long-range DNA interactions. Nat Cell Biol 13(8):944-51
abstractText  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.
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