TY - JOUR
T1 - Variegated gene expression caused by cell-specific long-range DNA interactions
AU - Noordermeer, D.
AU - de Wit, E.
AU - Klous, P.
AU - van de Werken, H.
AU - Simonis, M.
AU - Lopez-Jones, M.
AU - Eussen, B.
AU - Klein, A.M.
AU - Singer, R.H.
AU - de Laat, W.
N1 - Reporting year: 2011
Metis note: 3151580;
PY - 2011
Y1 - 2011
N2 - 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. [KEYWORDS: Animals, DNA/ genetics/ metabolism, GATA1 Transcription Factor/metabolism, Gene Expression, In Situ Hybridization, Fluorescence, Kruppel-Like Transcription Factors/metabolism, Locus Control Region, Mice, Mice, Transgenic, RNA, Messenger/genetics/metabolism, Transcriptional Activation, beta-Globins/genetics]
AB - 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. [KEYWORDS: Animals, DNA/ genetics/ metabolism, GATA1 Transcription Factor/metabolism, Gene Expression, In Situ Hybridization, Fluorescence, Kruppel-Like Transcription Factors/metabolism, Locus Control Region, Mice, Mice, Transgenic, RNA, Messenger/genetics/metabolism, Transcriptional Activation, beta-Globins/genetics]
U2 - 10.1038/ncb2278
DO - 10.1038/ncb2278
M3 - Article
SN - 1465-7392
VL - 13
SP - 944
EP - 951
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 8
ER -