Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
Epigenetics Chromatin. 2010 Jan 15;3(1):2. doi: 10.1186/1756-8935-3-2.
The field of epigenetics is developing rapidly, however we are only beginning to comprehend the complexity of its influence on gene regulation. Using genomic imprinting as a model we examine epigenetic profiles associated with different forms of gene regulation. Imprinting refers to the expression of a gene from only one of the chromosome homologues in a parental-origin-specific manner. This is dependent on heritable germline epigenetic control at a cis-acting imprinting control region that influences local epigenetic states. Epigenetic modifications associated with imprinting regulation can be compared to those associated with the more canonical developmental regulation, important for processes such as differentiation and tissue specificity. Here we test the hypothesis that these two mechanisms are associated with different histone modification enrichment patterns.
Using high-throughput data extraction with subsequent analysis, we have found that particular histone modifications are more likely to be associated with either imprinting repression or developmental repression of imprinted genes. H3K9me3 and H4K20me3 are together enriched at imprinted genes with differentially methylated promoters and do not show a correlation with developmental regulation. H3K27me3 and H3K4me3, however, are more often associated with developmental regulation. We find that imprinted genes are subject to developmental regulation through bivalency with H3K4me3 and H3K27me3 enrichment on the same allele. Furthermore, a specific tri-mark signature comprising H3K4me3, H3K9me3 and H4K20me3 has been identified at all imprinting control regions.
A large amount of data is produced from whole-genome expression and epigenetic profiling studies of cellular material. We have shown that such publicly available data can be mined and analysed in order to generate novel findings for categories of genes or regulatory elements. Comparing two types of gene regulation, imprinting and developmental, our results suggest that different histone modifications associate with these distinct processes. This form of analysis is therefore a useful tool to elucidate the complex epigenetic code associated with genome function and to determine the underlying features conferring epigenetic states.
表观遗传学领域发展迅速，但我们才刚刚开始理解其对基因调控影响的复杂性。我们以基因组印迹（genomic imprinting）为例，研究了与不同基因调控形式相关的表观遗传谱。印迹是指基因仅从亲本来源特异性的染色体同源物中的一条染色体上表达。这依赖于顺式作用印迹控制区的可遗传生殖系表观遗传控制，该控制区影响局部表观遗传状态。与印迹调控相关的表观遗传修饰可以与更典型的发育调控相关的修饰进行比较，这些修饰对于分化和组织特异性等过程很重要。在这里，我们假设这两种机制与不同的组蛋白修饰富集模式相关。
我们使用高通量数据提取和后续分析，发现特定的组蛋白修饰更可能与印迹抑制或印迹基因的发育抑制相关。H3K9me3 和 H4K20me3 在具有差异甲基化启动子的印迹基因中一起富集，并且与发育调控没有相关性。然而，H3K27me3 和 H3K4me3 更常与发育调控相关。我们发现印迹基因通过 H3K4me3 和 H3K27me3 富集在同一等位基因上的二价性而受到发育调控。此外，在所有印迹控制区都鉴定到了包含 H3K4me3、H3K9me3 和 H4K20me3 的特定三标记特征。
从细胞材料的全基因组表达和表观遗传谱研究中产生了大量的数据。我们已经表明，可以挖掘和分析这些公开可用的数据，以针对基因或调控元件的类别生成新的发现。通过比较两种类型的基因调控，印迹和发育，我们的结果表明，不同的组蛋白修饰与这些不同的过程相关。因此，这种分析形式是阐明与基因组功能相关的复杂表观遗传密码并确定赋予表观遗传状态的潜在特征的有用工具。
