Differentiation of developing olfactory neurons analysed in terms of coupled epigenetic landscapes

被引:12
作者
Alsing, Anne Katrine [1 ]
Sneppen, Kim [1 ]
机构
[1] Univ Copenhagen, Niels Bohr Inst, Ctr Models Life, DK-2100 Copenhagen, Denmark
基金
新加坡国家研究基金会;
关键词
RECEPTOR GENE CHOICE; MUTUALLY EXCLUSIVE EXPRESSION; SENSORY NEURONS; HISTONE ACETYLATION; NUCLEOSOME MODIFICATION; ODORANT RECEPTORS; IN-VIVO; MOUSE; EPITHELIUM; DYNAMICS;
D O I
10.1093/nar/gkt181
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The olfactory system integrates signals from receptors expressed in olfactory sensory neurons. Each sensory neuron expresses only one of many similar olfactory receptors (ORs). The choice of receptor is made stochastically early in the differentiation process and is maintained throughout the life of the neuron. The underlying mechanism of this stochastic commitment to one of multiple similar OR genes remains elusive. We present a theoretical analysis of a mechanism that invokes important epigenetic properties of the system. The proposed model combines nucleosomes and associated read-write enzymes as mediators of a cis-acting positive feedback with a trans-acting negative feedback, thereby coupling the local epigenetic landscape of the individual OR genes in a way that allow one and only one gene to be active at any time. The model pinpoint that singular gene selection does not require transient mechanisms, enhancer elements or transcription factors to separate choice from maintenance. In addition, our hypothesis allow us to combine all reported characteristics of singular OR gene selection, in particular that OR genes are silenced from OR transgenes. Intriguingly, it predicts that OR transgenes placed in close proximity should always be expressed simultaneously, though rarely.
引用
收藏
页码:4755 / 4764
页数:10
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