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

ABSTRACT: Mammalian genomes contain numerous regulatory DNA sites with unknown target genes. We used mice with an extra ?-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 ?-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.

SUBMITTER: Noordermeer D

PROVIDER: S-EPMC3151580 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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

Noordermeer Daan D de Wit Elzo E Klous Petra P van de Werken Harmen H Simonis Marieke M Lopez-Jones Melissa M Eussen Bert B de Klein Annelies A Singer Robert H RH de Laat Wouter W

Nature cell biology 20110626 8

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 genetical ...[more]

PMID: 21706023

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

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