Heterochromatin-mediated gene silencing facilitates the diversification of olfactory neurons.
Heterochromatin-mediated gene silencing facilitates the diversification of olfactory neurons.
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DOI：
10.1016/j.celrep.2014.10.001
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发表时间：
2014-11-06
期刊：
影响因子：
8.8
通讯作者：
Lomvardas S
中科院分区：
文献类型：
--
作者：
Lyons DB;Magklara A;Goh T;Sampath SC;Schaefer A;Schotta G;Lomvardas S
神经系统的一个惊人特性是其细胞多样性。这种多样性最初是由形态学和电生理学差异实现的，最终是由基因表达程序的变化产生的。在大多数情况下，这些变化由外部线索决定。然而，越来越多的神经元类型已被确定，其中诱导信号不能解释导致细胞多样化的少数但决定性的转录差异。在这里，我们发现，异染色质沉默，这是由组蛋白甲基转移酶G9a（KMT1C）和GLP（KMT1D），是必不可少的随机和奇异的OR表达。G9a和GLP的缺失显著降低了OR转录组的复杂性，导致由少数OR控制转录，并导致OR表达中的奇异性丧失。因此，除了其先前已知的功能，我们的数据表明，异染色质创建一个表观遗传平台，提供随机的，互斥的基因选择，并促进细胞多样性。
An astounding property of the nervous system is its cellular diversity. This diversity, which was initially realized by morphological and electrophysiological differences, is ultimately produced by variations in gene expression programs. In most cases these variations are determined by external cues. However, a growing number of neuronal types have been identified in which inductive signals cannot explain the few but decisive transcriptional differences that cause cell diversification. Here, we show that heterochromatic silencing, which we find is governed by histone methyltransferases G9a (KMT1C) and GLP (KMT1D), is essential for stochastic and singular OR expression. Deletion of G9a and GLP dramatically reduces the complexity of the OR transcriptome, resulting in transcriptional domination by a few ORs and loss of singularity in OR expression. Thus, in addition to its previously known functions, our data suggest that heterochromatin creates an epigenetic platform that affords stochastic, mutually exclusive gene choices and promotes cellular diversity.
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