MRC Human Genetics Unit, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XU, UK.
Genome Biol. 2017 Dec 28;18(1):242. doi: 10.1186/s13059-017-1379-8.
Enhancers are modular regulatory elements that are central to the spatial and temporal regulation of gene expression. Bidirectional transcription initiating at enhancers has been proposed to mark active enhancers and as such has been utilized to experimentally identify active enhancers de novo.
Here, we show that bidirectional transcription initiation is a pervasive feature of accessible chromatin, including at enhancers, promoters, and other DNase hypersensitive regions not marked with canonical histone modification profiles. Transcription is less predictive for enhancer activity than epigenetic modifications such as H3K4me1 or the accessibility of DNA when measured both in enhancer assays and at endogenous loci. The stability of enhancer initiated transcripts does not influence measures of enhancer activity and we cannot detect evidence of purifying selection on the resulting enhancer RNAs within the human population.
Our results indicate that bidirectional transcription initiation from accessible chromatin is not sufficient for, nor specific to, enhancer activity. Transcription initiating at enhancers may be a frequent by-product of promiscuous RNA polymerase initiation at accessible chromatin and is unlikely to generally play a functional role in enhancer activity.
增强子是模块化的调控元件，对基因表达的时空调控至关重要。从增强子起始的双向转录已被提出可标记活性增强子，并因此被用于实验性地从头鉴定活性增强子。
在这里，我们表明双向转录起始是可及染色质的普遍特征，包括增强子、启动子和其他没有经典组蛋白修饰谱标记的 DNase 超敏区域。与组蛋白修饰（如 H3K4me1）或 DNA 可及性相比，转录对增强子活性的预测性较差，无论是在增强子测定中还是在内源性基因座中测量。增强子起始转录本的稳定性并不影响增强子活性的测量，我们也不能在人类群体中检测到对产生的增强子 RNA 进行纯化选择的证据。
我们的结果表明，来自可及染色质的双向转录起始不足以也不是特异性地决定增强子活性。从增强子起始的转录可能是 RNA 聚合酶在可及染色质上随机起始的常见副产物，不太可能普遍在增强子活性中发挥功能作用。
