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

Natalia Stec, Katja Doerfel, Kelly Hills-Muckey, Victoria M. Ettorre, Sevinc Ercan, Wolfgang Keil, Christopher M. Hammell

Research output: Contribution to journalArticlepeer-review

Abstract

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. Stec et al. describe a novel transcriptional priming mechanism where BLMP-1, a highly conserved ZnF transcription factor, decompacts chromatin at specific target loci hours prior to gene expression. This mechanism regulates the transcriptional output of many key genes that control cell fate specification during post-embryonic development.

Original languageEnglish (US)
Pages (from-to)809-826.e6
JournalCurrent Biology
Volume31
Issue number4
DOIs
StatePublished - Feb 22 2021

Keywords

  • oscillatory transcription
  • pioneer transcription factor
  • temporal patterning
  • transcriptional activation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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