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Enhancer-promoter interactions become more instructive in the transition from cell-fate specification to tissue differentiation.


ABSTRACT: To regulate expression, enhancers must come in proximity to their target gene. However, the relationship between the timing of enhancer-promoter (E-P) proximity and activity remains unclear, with examples of uncoupled, anticorrelated and correlated interactions. To assess this, we selected 600 characterized enhancers or promoters with tissue-specific activity in Drosophila embryos and performed Capture-C in FACS-purified myogenic or neurogenic cells during specification and tissue differentiation. This enabled direct comparison between E-P proximity and activity transitioning from OFF-to-ON and ON-to-OFF states across developmental conditions. This showed remarkably similar E-P topologies between specified muscle and neuronal cells, which are uncoupled from activity. During tissue differentiation, many new distal interactions emerge where changes in E-P proximity reflect changes in activity. The mode of E-P regulation therefore appears to change as embryogenesis proceeds, from largely permissive topologies during cell-fate specification to more instructive regulation during terminal tissue differentiation, when E-P proximity is coupled to activation.

SUBMITTER: Pollex T 

PROVIDER: S-EPMC11018526 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Enhancer-promoter interactions become more instructive in the transition from cell-fate specification to tissue differentiation.

Pollex Tim T   Rabinowitz Adam A   Gambetta Maria Cristina MC   Marco-Ferreres Raquel R   Viales Rebecca R RR   Jankowski Aleksander A   Schaub Christoph C   Furlong Eileen E M EEM  

Nature genetics 20240311 4


To regulate expression, enhancers must come in proximity to their target gene. However, the relationship between the timing of enhancer-promoter (E-P) proximity and activity remains unclear, with examples of uncoupled, anticorrelated and correlated interactions. To assess this, we selected 600 characterized enhancers or promoters with tissue-specific activity in Drosophila embryos and performed Capture-C in FACS-purified myogenic or neurogenic cells during specification and tissue differentiatio  ...[more]

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