Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.
Elife. 2018 Oct 26;7:e37344. doi: 10.7554/eLife.37344.
An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here, we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one stage. Based on nuclear transcription profiles, we define 15,714 protein-coding promoters and 19,231 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, more than 1000 promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements changes during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across life provides a platform for understanding how transcription controls development and ageing.
理解控制发育和生理的转录回路的一个重要步骤是全局识别和描述调控元件。在这里，我们展示了第一个跨越动物发育和衰老的调控元件图谱，鉴定了至少在一个阶段可及的 42,245 个元件。基于核转录谱，我们定义了 15,714 个蛋白编码启动子和 19,231 个推定增强子，并发现这两种类型的元件都可以驱动非定向转录。此外，超过 1000 个启动子产生与蛋白编码基因反义的转录本，这表明它们参与了广泛的调控机制。我们发现，大多数元件的可及性在发育和/或衰老过程中发生变化，并且可及性变化的模式与特定的发育或生理过程相关。跨越生命的调控元件图谱和特征为理解转录如何控制发育和衰老提供了一个平台。
