Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
BMC Bioinformatics. 2010 Nov 12;11:557. doi: 10.1186/1471-2105-11-557.
Epigenetics is an important layer of transcriptional control necessary for cell-type specific gene regulation. Recent studies have shown significant epigenetic patterns associated with developmental stages and diseases. However, previous studies have been mostly limited to focal epigenetic patterns, whereas methods for analyzing large-scale organizations are still lacking.
We developed a hidden Markov model (HMM) approach for detecting the types and locations of epigenetic domains from multiple histone modifications. We used this method to analyze a published ChIP-seq dataset of five histone modification marks (H3K4me2, H3K4me3, H3K27me3, H3K9me3, and H3K36me3) in mouse embryonic stem (ES) cells. We identified three types of domains, corresponding to active, non-active, and null states. In total, our three-state HMM identified 258 domains in the mouse genome containing 9.6 genes on average. These domains were validated by a number of criteria. The largest domains correspond to olfactory receptor (OR) gene clusters. Each Hox gene cluster also forms a separate epigenetic domain. We found that each type of domain is associated with distinct biological functions and structural changes during early cell differentiation.
The HMM approach successfully detects domains of consistent epigenetic patterns from ChIP-seq data, providing new insights into the role of epigenetics in long-range gene regulation.
表观遗传学是转录控制的一个重要层面，对于细胞类型特异性基因调控是必需的。最近的研究表明，与发育阶段和疾病相关的显著表观遗传模式。然而，以前的研究大多局限于焦点表观遗传模式，而分析大规模组织的方法仍然缺乏。
我们开发了一种隐马尔可夫模型（HMM）方法，用于从多个组蛋白修饰中检测表观遗传域的类型和位置。我们使用这种方法分析了已发表的小鼠胚胎干细胞（ES 细胞）中五种组蛋白修饰标记（H3K4me2、H3K4me3、H3K27me3、H3K9me3 和 H3K36me3）的 ChIP-seq 数据集。我们鉴定了三种类型的域，分别对应于活跃、非活跃和空状态。总的来说，我们的三状态 HMM 在小鼠基因组中鉴定了 258 个包含平均 9.6 个基因的域。这些域通过多种标准进行了验证。最大的域对应于嗅觉受体（OR）基因簇。每个 Hox 基因簇也形成一个单独的表观遗传域。我们发现，每种类型的域都与早期细胞分化过程中独特的生物学功能和结构变化相关。
HMM 方法成功地从 ChIP-seq 数据中检测到一致的表观遗传模式的域，为表观遗传学在长距离基因调控中的作用提供了新的见解。
