4.8 Article

An Epigenetic Priming Mechanism Mediated by Nutrient Sensing Regulates Transcriptional Output during C. elegans Development

Journal

CURRENT BIOLOGY
Volume 31, Issue 4, Pages 809-+

Publisher

CELL PRESS
DOI: 10.1016/j.cub.2020.11.060

Keywords

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Funding

  1. ATIP/Avenir Young Investigator program of the CNRS
  2. NIH [R35NS105094]
  3. NSF [PHY 1502151]
  4. Human Frontier Science Program (HFSP) [LT000250/2013-C]
  5. Rita Allen Foundation
  6. NIH NIGMS [R01GM117406]
  7. Cold Spring Harbor Laboratory

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Precise tuning of gene expression levels is critical for most developmental pathways. BLMP-1/Blimp1 acts as a pioneer factor to decompact chromatin near its target loci during embryogenesis and regulates subsequent target gene transcription during post-embryonic development. This priming mechanism can be genetically separated and maintained through nutrient sensing, integrating transcriptional output with environmental conditions.
Although precise tuning of gene expression levels is critical for most developmental pathways, the mechanisms by which the transcriptional output of dosage-sensitive molecules is established or modulated by the environment remain poorly understood. Here, we provide a mechanistic framework for how the conserved transcription factor BLMP-1/Blimp1 operates as a pioneer factor to decompact chromatin near its target loci during embryogenesis (hours prior to major transcriptional activation) and, by doing so, regulates both the duration and amplitude of subsequent target gene transcription during post-embryonic development. This priming mechanism is genetically separable from the mechanisms that establish the timing of transcriptional induction and functions to canalize aspects of cell-fate specification, animal size regulation, and molting. A key feature of the BLMP-1-dependent transcriptional priming mechanism is that chromatin decompaction is initially established during embryogenesis and maintained throughout larval development by nutrient sensing. This anticipatory mechanism integrates transcriptional output with environmental conditions and is essential for resuming normal temporal patterning after animals exit nutrient-mediated developmental arrests.

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