Enhancer interaction networks as a means for singular olfactory receptor expression.

Enhancer interaction networks as a means for singular olfactory receptor expression.
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DOI:
10.1016/j.cell.2014.09.033
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发表时间:
2014-10-23
期刊:
影响因子:
64.5
通讯作者:
Lomvardas S
Lomvardas S
中科院分区:
生物学1区
文献类型:
--
作者:
Markenscoff-Papadimitriou E;Allen WE;Colquitt BM;Goh T;Murphy KK;Monahan K;Mosley CP;Ahituv N;Lomvardas S

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大约2800个嗅觉受体(OR)等位基因中的一个的转录激活是一个知之甚少的过程。在这里,我们确定了过多的假定或增强剂,并研究其在嗅觉神经元的体内活性。通过不寻常的表观遗传特征区分,候选OR增强子的特征在于与OR转录相关的广泛的染色体间相互作用,并且共享类似的转录因子足迹模式。特别是,我们建立的作用,转录因子Bptf作为一个促进者的增强子相互作用和OR转录。我们的观察结果与模型一致,即OR转录发生在多个相互作用的增强子的背景下。这些染色体间相互作用的破坏导致弱的和多基因的OR表达,这表明在随机选择的OR上的许多增强子的罕见巧合可以解释OR转录的奇异性和鲁棒性。
The transcriptional activation of one out of ~2800 olfactory receptor (OR) alleles is a poorly understood process. Here, we identify a plethora of putative OR enhancers and study their in vivo activity in olfactory neurons. Distinguished by an unusual epigenetic signature, candidate OR enhancers are characterized by extensive interchromosomal interactions associated with OR transcription and share the similar pattern of transcription factor footprints. In particular, we establish the role of the transcription factor Bptf as a facilitator of both enhancer interactions and OR transcription. Our observations agree with the model whereby OR transcription occurs in the context of multiple interacting enhancers. Disruption of these interchromosomal interactions results in weak and multigenic OR expression, suggesting that the rare coincidence of numerous enhancers over a stochastically chosen OR may account for the singularity and robustness in OR transcription.
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