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

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

doi:10.1038/ncb2278

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

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

Cell Biology

Research output: Contribution to journal › Article › peer-review

130 Scopus citations

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.

Original language	English (US)
Pages (from-to)	944-951
Number of pages	8
Journal	Nature Cell Biology
Volume	13
Issue number	8
DOIs	https://doi.org/10.1038/ncb2278
State	Published - Aug 2011

ASJC Scopus subject areas

Cell Biology

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10.1038/ncb2278

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title = "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 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.",

author = "Daan Noordermeer and {De Wit}, Elzo and Petra Klous and {Van De Werken}, Harmen and Marieke Simonis and Melissa Lopez-Jones and Bert Eussen and {De Klein}, Annelies and Singer, {Robert H.} and {De Laat}, Wouter",

note = "Funding Information: We thank J. Marteijn and W. Vermeulen for providing Rad23a knockout material, Y. Oz for counting FISH slides, V. Buckle for providing BAC probes, J. van Rheenen and the Hubrecht Imaging Center for help with image analysis and E. Splinter and other members of the group for assistance. This work was financially supported by",

year = "2011",

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doi = "10.1038/ncb2278",

language = "English (US)",

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AU - Noordermeer, Daan

AU - De Wit, Elzo

AU - Klous, Petra

AU - Van De Werken, Harmen

AU - Simonis, Marieke

AU - Lopez-Jones, Melissa

AU - Eussen, Bert

AU - De Klein, Annelies

AU - Singer, Robert H.

AU - De Laat, Wouter

N1 - Funding Information: We thank J. Marteijn and W. Vermeulen for providing Rad23a knockout material, Y. Oz for counting FISH slides, V. Buckle for providing BAC probes, J. van Rheenen and the Hubrecht Imaging Center for help with image analysis and E. Splinter and other members of the group for assistance. This work was financially supported by

PY - 2011/8

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N2 - 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.

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

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