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| Format: | Recurso digital |
| Language: | English |
| Published: |
Zenodo
2026
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| Subjects: | |
| Online Access: | https://doi.org/10.5281/zenodo.16745299 |
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Table of Contents:
- <p><em>Schistosoma mansoni</em> is a parasitic flatworm that has two, genetically determined, sexes. We used aggregated data of 8 posttranslational histone modifications (ChIP-Seq), chromatin accessibility (ATAC-Seq), transcription (RNA-Seq) and genome feature annotations to decipher the histone code of genes involved in the differentiation of schistosome gonads such as the ovary of females and testes of males <em>S. mansoni</em>. We show that (i) schistosome gonads possess at least two classes of protein coding genes: H3K4me3-positive genes that display canonical features of eukaryotic protein-coding genes such as peaks of H3K4me3 at the transcription start sites (TSS) and increase of histone acetylation towards the transcription end site (TES), but also a non-canonical H3K9/27me3 plateau just upstream of the TSS. H3K4me3 enrichment at the TSS is highly predictive for transcription strength in these genes compared to a second class of protein coding genes (H3K4me3-negative genes) that does not display this pattern and is characterized by absence of the investigated histone marks at TSS and TES. This is indicative for the existence of hitherto unknown, potentially schistosome-specific histone marks in these genes. The absence of <a>H3K4me3 at the TSS </a>is not associated with inducible or stable genes in the gonads. Instead, gene ontology analysis indicates that H3K4me3-positive genes are related to intracellular functions typically govern processes such as metabolism or signal transduction while H3K4me3-negative genes are dedicated to intercellular functions such as cell communication or immune responses. (ii) Individual histone modifications and combinations of them are associated with functional features of the schistosome genome, something known as “chromatin colours”. In H3K4me3-positive genes, there is clear co-linearity of 3 colours, which strongly suggests a functional role of histone modifications in the control of transcription pre-initiation, promotor release, and transcription termination. (iii) There are striking chromatin structure changes during maturation of the gonads in all genomic features including protein-coding and non-protein coding genes as well as repetitive sequences. The nature of these changes is different in both sexes. H3K36me3 and H3K9me3, and H3K23ac and H3K9ac show the strongest variations. (iv) Pharmacological inhibition of <a>histone demethylation activity by IOX1 </a>leads to a concentration-dependent separation (“divorce”) of schistosome <a>couples</a> confirming the importance of H3K36/H3K9 methylation for pairing maintenance and indicating histone demethylase as a potential <a>drug target</a>, albeit of limited practical interest due to high homology to the human enzyme arguing for the search for schistosoma-specific histone modifications. Collectively, our findings offer unprecedented insights into histone codes and chromatin dynamics governing the reproductive development of <em>S. mansoni</em> gonads.</p> <p>Made at IHPE.</p>