Abstract
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.
Highlights
Gene expression is tightly controlled in eukaryotic cells by the composition, organization and dynamics of nucleosomes, consisting of an octamer of histone proteins wrapped in ~146bp of DNA
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
Using the epigenomic profiling method Cut&Run with a dedicated data analysis approach, we unexpectedly found that dhd is embedded in an unusual chromatin mini-domain featuring repressive histone modifications H3K27me3 and H3K9me3 and flanked by two regulatory elements
Summary
Gene expression is tightly controlled in eukaryotic cells by the composition, organization and dynamics of nucleosomes, consisting of an octamer of histone proteins wrapped in ~146bp of DNA. The resulting chromatin landscape is further organized by insulator proteins that delimit tridimensional contacts along the genome, forming sub-nuclear domains and guiding contacts between promoters and their cognate regulatory elements [4]. This tightly regulated epigenomic environment profoundly influences RNA Polymerase access to DNA and transcriptional activity. A privileged method is ablation or dosage manipulation of each component to measure its impact on gene expression While these approaches can yield precious functional insight, the ubiquitous expression and wide range of activities of these factors, as well as redundancies in their interactions, make it difficult to infer their precise function. We previously described one of such cases, where perturbation of the histone H3K4 demethylase Lid/KDM5 or the histone deacetylase complex Sin3A/Rpd in Drosophila ovaries dramatically abrogated the expression of the maternal gene deadhead (dhd), which is essential for female fertility [5]
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