No abstract

Enhancers confer precise spatiotemporal patterns of gene expression in response to developmental and environmental stimuli. Over the last decade, the transcription of enhancer RNAs (eRNAs) – nascent RNAs transcribed from active enhancers – has emerged as a key factor regulating enhancer activity. eRNAs are relatively short-lived RNA species that are transcribed at very high rates but also quickly degraded. Nevertheless, eRNAs are deeply intertwined within enhancer regulatory networks and are implicated in a number of transcriptional control mechanisms. Enhancers show changes in function and sequence over evolutionary time, raising questions about the relationship between enhancer sequences and eRNA function. Moreover, the vast majority of single nucleotide polymorphisms associated with human complex diseases map to the non-coding genome, with causal disease variants enriched within enhancers. In this Primer, we survey the diverse roles played by eRNAs in enhancer-dependent gene expression, evaluating different models for eRNA function. We also explore questions surrounding the genetic conservation of enhancers and how this relates to eRNA function and dysfunction.

Much of the effort toward building resilience has been directed at identifying appropriate metrics and indicators of system resilience, and from this, interventions to strengthen resilience. An essential ingredient of such resilience-building efforts is to apply public processes of dialogue and diagnosis to identify systems fragility and potential for failure. Social learning processes allow people to take new perspectives in understanding their own and other's interests and values, to identify problems and formulate solutions by focusing on the potential for systemic failure. Diagnosis and dialogue tools used in a participatory process in Northern Thailand included food systems mapping, identifying potential points of failure within systems, and applying a self-assessment tool structured around resilience characteristics. This process proved important for developing stakeholder understanding of systems thinking and of concepts of resilience. Yet it is a process that is not without challenges. We noted the difficulty with defining food system boundaries and the tendency for participants to persist with familiar understandings of problems within their sector, with it taking time to shift to thinking about points of fragility within the whole system. We particularly recognize the participatory process itself as being of value, in addition to the specific outcomes such as risk identification or interventions for resilience.