Sinha Puja, Singh Kiran, Sachan Manisha
Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad, 211004, India.
Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India.
BMC Mol Biol. 2017 Jan 11;18(1):1. doi: 10.1186/s12867-016-0078-4.
DNA methylation is a major epigenetic modification, playing a crucial role in the development and differentiation of higher organisms. DNA methylation is also known to regulate transcription by gene repression. Various developmental genes such as c-mos, HoxB5, Sox11, and Sry show tissue-specific gene expression that was shown to be regulated by promoter DNA methylation. The aim of the present study is to investigate the establishment of chromatin marks (active or repressive) in relation to heterogeneous methylation in the promoter regions of these developmentally important genes.
Chromatin-immunoprecipitation (ChIP) assays were performed to immuno-precipitate chromatin by antibodies against both active (H3K4me3) and repressive (H3K9me3) chromatin regions. The analysis of ChIP results showed that both the percentage input and fold enrichment of activated chromatin was higher in tissues expressing the respective genes as compared to the tissues not expressing the same set of genes. This was true for all the genes selected for the study (c-mos, HoxB5, Sox11, and Sry). These findings illustrate that inconsistent DNA methylation patterns (sporadic, mosaic and heterogeneous) may also influence gene regulation, thereby resulting in the modulation of chromatin conformation.
These findings illustrate that various patterns of DNA methylation (asynchronous, mosaic and heterogeneous) correlates with chromatin modification, resulting in the gene regulation.
DNA甲基化是一种主要的表观遗传修饰，在高等生物的发育和分化中起关键作用。已知DNA甲基化还通过基因抑制来调节转录。各种发育基因，如c-mos、HoxB5、Sox11和Sry，表现出组织特异性基因表达，已证明其受启动子DNA甲基化调控。本研究的目的是研究与这些发育重要基因启动子区域的异质性甲基化相关的染色质标记（活性或抑制性）的建立。
进行染色质免疫沉淀（ChIP）分析，用针对活性（H3K4me3）和抑制性（H3K9me3）染色质区域的抗体免疫沉淀染色质。ChIP结果分析表明，与不表达相同基因集的组织相比，表达相应基因的组织中活化染色质的输入百分比和富集倍数均更高。本研究选择的所有基因（c-mos、HoxB5、Sox11和Sry）均是如此。这些发现表明，不一致的DNA甲基化模式（散在、镶嵌和异质性）也可能影响基因调控，从而导致染色质构象的调节。
这些发现表明，各种DNA甲基化模式（异步、镶嵌和异质性）与染色质修饰相关，从而导致基因调控。
