Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Nat Cell Biol. 2011 Jun 26;13(8):944-51. doi: 10.1038/ncb2278.
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.
哺乳动物基因组包含大量具有未知靶基因的调控 DNA 位点。我们使用带有额外的β-珠蛋白基因调控区（LCR）的小鼠来研究调控因子如何在基因组中寻找靶基因。我们发现 LCR 会在核内的一个受限亚区中进行采样，在此区域内，它优先与受共享转录因子控制的基因发生接触。除了位于另一条染色体上的内源性β-珠蛋白基因外，没有可检测到的被接触基因被显著上调。这从遗传学上证明了哺乳动物的转录激活是可能的，但表明这种情况很少见。转录激活不是全细胞性的，而是发生在富含染色体间相互作用的“ jackpot”细胞中。因此，细胞特异性的长距离 DNA 接触可以导致斑驳的表达。
