Department of Medicine, Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York Presbyterian Hospital, New York, New York, United States of America.
Division of Genomics, Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States of America.
PLoS Genet. 2023 Jan 19;19(1):e1010567. doi: 10.1371/journal.pgen.1010567. eCollection 2023 Jan.
It is a generally accepted model that environmental influences can exert their effects, at least in part, by changing the molecular regulators of transcription that are described as epigenetic. As there is biochemical evidence that some epigenetic regulators of transcription can maintain their states long term and through cell division, an epigenetic model encompasses the idea of maintenance of the effect of an exposure long after it is no longer present. The evidence supporting this model is mostly from the observation of alterations of molecular regulators of transcription following exposures. With the understanding that the interpretation of these associations is more complex than originally recognised, this model may be oversimplistic; therefore, adopting novel perspectives and experimental approaches when examining how environmental exposures are linked to phenotypes may prove worthwhile. In this review, we have chosen to use the example of nonalcoholic fatty liver disease (NAFLD), a common, complex human disease with strong environmental and genetic influences. We describe how epigenomic approaches combined with emerging functional genetic and single-cell genomic techniques are poised to generate new insights into the pathogenesis of environmentally influenced human disease phenotypes exemplified by NAFLD.
这是一个被普遍接受的模式，即环境影响可以通过改变被描述为表观遗传的转录分子调节剂来发挥作用，至少在某种程度上是这样。由于有生化证据表明，一些转录的表观遗传调节剂可以长期保持其状态，并通过细胞分裂来维持，因此表观遗传模型包含了在暴露不再存在后很长一段时间内保持暴露效应的想法。支持这种模式的证据主要来自于观察暴露后转录的分子调节剂的变化。由于认识到这些关联的解释比最初认识到的要复杂得多，因此这种模式可能过于简单化；因此，在研究环境暴露与表型之间的关系时，采用新颖的视角和实验方法可能是值得的。在这篇综述中，我们选择了非酒精性脂肪性肝病（NAFLD）作为例子，这是一种常见的复杂人类疾病，具有强烈的环境和遗传影响。我们描述了表观基因组学方法如何与新兴的功能遗传和单细胞基因组技术相结合，为环境影响的人类疾病表型的发病机制提供新的见解，以 NAFLD 为例。
