Abstract
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 Caenorhabditis elegans 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 C. elegans life provides a platform for understanding how transcription controls development and ageing.
Highlights
The genome encodes the information for organismal life
Because different transcriptional programs operate in different periods of life and ageing.C. elegans is ideal for addressing this question, as it has a simple anatomy, well defined cell types, and short development and lifespan
Micrococcal nuclease (MNase) data were collected for the embryo stage
Summary
The genome encodes the information for organismal life. Because the deployment of genomic information depends in large part on regulatory elements such as promoters and enhancers, their identification and characterization is essential for understanding genome function and its regulation.Regulatory elements are typically depleted for nucleosomes, which facilitates their identification using sensitivity to digestion by nucleases such as DNase I or Tn5 transposase, termed DNA accessibility (Sabo et al 2006; Crawford et al 2006; Buenrostro et al 2013). Large repertoires of regulatory elements have been determined by profiling DNA accessibility genome-wide in different cell types and developmental stages (Thomas et al 2011; Kharchenko et al 2011; Thurman et al 2012; Yue et al 2014; Roadmap Epigenomics Consortium et al 2015; Daugherty et al 2017; Ho et al 2017). No study has yet investigated regulatory element usage across the life of an animal, from the embryo to the end of life. Such information is important, because different transcriptional programs operate in different periods of life and ageing.C. elegans is ideal for addressing this question, as it has a simple anatomy, well defined cell types, and short development and lifespan. A map of regulatory elements and their temporal dynamics would facilitate understanding of the genetic control of organismal life
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