Department of Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania, United States of America.
PLoS One. 2012;7(10):e46867. doi: 10.1371/journal.pone.0046867. Epub 2012 Oct 9.
The epigenetic contribution to neurogenesis is largely unknown. There is, however, growing evidence that posttranslational modification of histones is a dynamic process that shows many correlations with gene expression. Here we have followed the genome-wide distribution of two important histone H3 modifications, H3K4me2 and H3K27me3 during late mouse retina development. The retina provides an ideal model for these studies because of its well-characterized structure and development and also the extensive studies of the retinal transcriptome and its development. We found that a group of genes expressed only in mature rod photoreceptors have a unique signature consisting of de-novo accumulation of H3K4me2, both at the transcription start site (TSS) and over the whole gene, that correlates with the increase in transcription, but no accumulation of H3K27me3 at any stage. By in silico analysis of this unique signature we have identified a larger group of genes that may be selectively expressed in mature rod photoreceptors. We also found that the distribution of H3K4me2 and H3K27me3 on the genes widely expressed is not always associated with their transcriptional levels. Different histone signatures for retinal genes with the same gene expression pattern suggest the diversities of epigenetic regulation. Genes without H3K4me2 and H3K27me3 accumulation at any stage represent a large group of transcripts never expressed in retina. The epigenetic signatures defined by H3K4me2 and H3K27me3 can distinguish cell-type specific genes from widespread transcripts and may be reflective of cell specificity during retina maturation. In addition to the developmental patterns seen in wild type retina, the dramatic changes of histone modification in the retinas of mutant animals lacking rod photoreceptors provide a tool to study the epigenetic changes in other cell types and thus describe a broad range of epigenetic events in a solid tissue in vivo.
表观遗传对神经发生的贡献在很大程度上是未知的。然而，越来越多的证据表明，组蛋白的翻译后修饰是一个动态过程，与基因表达有许多相关性。在这里，我们跟踪了两种重要的组蛋白 H3 修饰（H3K4me2 和 H3K27me3）在晚期小鼠视网膜发育过程中的全基因组分布。视网膜为这些研究提供了一个理想的模型，因为它具有良好的特征结构和发育，并且对视网膜转录组及其发育的研究也很广泛。我们发现，一组仅在成熟的杆状光感受器中表达的基因具有独特的特征，即 H3K4me2 的从头积累，无论是在转录起始位点（TSS）还是整个基因上，这与转录的增加相关，但在任何阶段都没有 H3K27me3 的积累。通过对这种独特特征的计算机分析，我们确定了一组可能在成熟的杆状光感受器中选择性表达的更大的基因。我们还发现，在广泛表达的基因上 H3K4me2 和 H3K27me3 的分布并不总是与其转录水平相关。具有相同基因表达模式的视网膜基因的不同组蛋白特征表明了表观遗传调控的多样性。在任何阶段都没有 H3K4me2 和 H3K27me3 积累的基因代表了一组从未在视网膜中表达的转录本。H3K4me2 和 H3K27me3 定义的表观遗传特征可以将细胞类型特异性基因与广泛表达的转录本区分开来，并且可能反映了视网膜成熟过程中的细胞特异性。除了在野生型视网膜中观察到的发育模式外，缺乏杆状光感受器的突变动物的视网膜中组蛋白修饰的剧烈变化为研究其他细胞类型中的表观遗传变化提供了工具，从而描述了在体内实体组织中的广泛的表观遗传事件。
