Developmental Transcriptional Enhancers: A Subtle Interplay between Accessibility and Activity: Considering Quantitative Accessibility Changes between Different Regulatory States of an Enhancer Deconvolutes the Complex Relationship between Accessibility and Activity. (6th March 2020)

• Record Type: Journal Article
• Authors: Bozek, Marta; Gompel, Nicolas
• Is Part Of: BioEssays. Volume 42:Number 4(2020:Apr.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-03-06
• Subjects: accessibility -- ATAC‐seq -- chromatin -- embryonic development -- enhancer -- quantitative analysis -- transcriptional regulation; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.201900188
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract: Measurements of open chromatin in specific cell types are widely used to infer the spatiotemporal activity of transcriptional enhancers. How reliable are these predictions? In this review, it is argued that the relationship between the accessibility and activity of an enhancer is insufficiently described by simply considering open versus closed chromatin, or active versus inactive enhancers. Instead, recent studies focusing on the quantitative nature of accessibility signal reveal subtle differences between active enhancers and their different inactive counterparts: the closed silenced state and the accessible primed and repressed states. While the open structure as such is not a specific indicator of enhancer activity, active enhancers display a higher degree of accessibility than the primed and repressed states. Molecular mechanisms that may account for these quantitative differences are discussed. A model that relates molecular events at an enhancer to changes in its activity and accessibility in a developing tissue is also proposed. Abstract : While active enhancers are characterized by open chromatin structure, not all open enhancers are active. The binary distinction into open/closed regions and active/inactive enhancers is insufficient to describe this complex relationship. Instead, considering quantitative differences in the accessibility signal allows for discriminating between different regulatory states.