Lyons David B, Magklara Angeliki, Goh Tracie, Sampath Srihari C, Schaefer Anne, Schotta Gunnar, Lomvardas Stavros
Tetrad Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Division of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 45110 Ioannina, Greece.
Cell Rep. 2014 Nov 6;9(3):884-92. doi: 10.1016/j.celrep.2014.10.001. Epub 2014 Oct 30.
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 olfactory receptor (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, our data suggest that, in addition to its previously known functions, heterochromatin creates an epigenetic platform that affords stochastic, mutually exclusive gene choices and promotes cellular diversity.
神经系统一个令人惊奇的特性是其细胞多样性。这种多样性最初是通过形态学和电生理学差异得以认识的，最终是由基因表达程序的变化产生的。在大多数情况下，这些变化由外部信号决定。然而，已鉴定出越来越多的神经元类型，其中诱导信号无法解释导致细胞多样化的少数但决定性的转录差异。在这里，我们表明异染色质沉默对于随机且单一的嗅觉受体（OR）表达至关重要，我们发现它受组蛋白甲基转移酶G9a（KMT1C）和GLP（KMT1D）调控。删除G9a和GLP会显著降低OR转录组的复杂性，导致少数OR在转录上占主导地位以及OR表达失去单一性。因此，我们的数据表明，除了其先前已知的功能外，异染色质创建了一个表观遗传平台，提供随机、相互排斥的基因选择并促进细胞多样性。
