Three classes of epigenomic regulators converge to hyperactivate the essential maternal gene deadhead within a heterochromatin mini-domain

PLoS Genet. 2022 Jan 4;18(1):e1009615. doi: 10.1371/journal.pgen.1009615. eCollection 2022 Jan.


The formation of a diploid zygote is a highly complex cellular process that is entirely controlled by maternal gene products stored in the egg cytoplasm. This highly specialized transcriptional program is tightly controlled at the chromatin level in the female germline. As an extreme case in point, the massive and specific ovarian expression of the essential thioredoxin Deadhead (DHD) is critically regulated in Drosophila by the histone demethylase Lid and its partner, the histone deacetylase complex Sin3A/Rpd3, via yet unknown mechanisms. Here, we identified Snr1 and Mod(mdg4) as essential for dhd expression and investigated how these epigenomic effectors act with Lid and Sin3A to hyperactivate dhd. Using Cut&Run chromatin profiling with a dedicated data analysis procedure, we found that dhd is intriguingly embedded in an H3K27me3/H3K9me3-enriched mini-domain flanked by DNA regulatory elements, including a dhd promoter-proximal element essential for its expression. Surprisingly, Lid, Sin3a, Snr1 and Mod(mdg4) impact H3K27me3 and this regulatory element in distinct manners. However, we show that these effectors activate dhd independently of H3K27me3/H3K9me3, and that dhd remains silent in the absence of these marks. Together, our study demonstrates an atypical and critical role for chromatin regulators Lid, Sin3A, Snr1 and Mod(mdg4) to trigger tissue-specific hyperactivation within a unique heterochromatin mini-domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / physiology*
  • Epigenomics
  • Female
  • Gene Expression Regulation
  • Heterochromatin / chemistry
  • Heterochromatin / genetics*
  • Histone Demethylases / metabolism*
  • Histones / metabolism
  • Male
  • Maternal Inheritance
  • Membrane Proteins / genetics*
  • Organ Specificity
  • Ovary / chemistry
  • Promoter Regions, Genetic
  • RNA-Binding Proteins / metabolism*
  • Regulatory Elements, Transcriptional
  • Sin3 Histone Deacetylase and Corepressor Complex / metabolism*
  • Thioredoxins / genetics*
  • Transcription Factors / metabolism*


  • DHD protein, Drosophila
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Heterochromatin
  • Histones
  • Membrane Proteins
  • RNA-Binding Proteins
  • SIN3A transcription factor
  • Snr1 protein, Drosophila
  • Transcription Factors
  • histone H3 trimethyl Lys4
  • mod protein, Drosophila
  • Thioredoxins
  • Histone Demethylases
  • Lid protein, Drosophila
  • Sin3 Histone Deacetylase and Corepressor Complex

Grant support

This work was supported by an Association pour la Recherche sur le Cancer (ARC) Foundation grant (PJA20191209671) to BL. DTC was supported by a PhD fellowship from the Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation and from the ARC (ARCDOC42020020001727). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.