235: Maternal H3K9 methyltransferases control aRMAE in C. elegans

Sands et al., Nature Communications - Using dual-color reporters in C. elegans, the study shows maternal H3K9 methyltransferases MET-2 and SET-25 antagonistically regulate autosomal random monoallelic expression initiated in the early embryo. Key terms: histone-methyltransferase, aRMAE, MET-2, SET-25, c-elegans. Study Highlights:Dual-color fluorescent reporter alleles in C. elegans intestine cells enabled single-cell quantification of allele expression and a targeted screen for aRMAE regulators. MET-2/SETDB1, with LIN-65 and ARLE-14, acts maternally in the 8-cell E-cell to prevent monoallelic expression, while SET-25/SUV39 with HPL-2 and LIN-61 promotes allele silencing. Catalytic SET domains of both MET-2 and SET-25 are required for their opposing activities, and loss of MET-2 increases persistent but non-heritable monoallelic expression whereas loss of SET-25 causes biallelic expression. Reciprocal crosses and genetic interactions indicate these maternal H3K9 HMTs set early embryonic histone states that are propagated through somatic divisions to shape tissue-wide allele expression. Conclusion:Maternal MET-2 and SET-25 establish competing H3K9-related chromatin states in the early embryo that bias autosomal alleles toward persistent somatic monoallelic or biallelic expression Music:Enjoy the music based on this article at the end of the episode. Article title:Maternal histone methyltransferases antagonistically regulate autosomal random monoallelic expression (aRMAE) in C. elegans First author:Sands Journal:Nature Communications DOI:10.1038/s41467-025-66501-5 Reference:Sands, B., Yun, S.R., Oshima, J. et al. Maternal histone methyltransferases antagonistically regulate autosomal random monoallelic expression (aRMAE) in C. elegans. Nat Commun (2025). https://doi.org/10.1038/s41467-025-66501-5 License:CC BY 4.0 International License Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/maternal-h3k9-armae-c-elegans QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-21. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited transcript sections describing MAE basics, the C. elegans reporter MAE assay, intrinsic noise as a MAE metric, the MET-2/SET-25 antagonism and cofactors, maternal deposition in the E-cell, catalytic SET-domain requirements, cross experiments, gene specificity, and translational implications.- transcript topics: Introduction to autosomal random monoallelic expression (aRMAE); C. elegans MAE reporter system with dual-color alleles (hsp-90); Intrinsic noise as a quantitative MAE measure; RNAi screen identifying H3K9 methyltransferases MET-2 and SET-25; Antagonistic roles of MET-2 (negative regulator) and SET-25 (positive regulator) of MAE; Cofactors LIN-65, ARLE-14, HPL-2, LIN-61 QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 8- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- Autosomal random monoallelic expression (aRMAE) is probabilistic, persistent within a tissue, but not heritable across generations.- In C. elegans intestine, maternal MET-2 antagonizes SET-25 to regulate MAE; MET-2 promotes biallelic expression while SET-25 promotes m... Chapters (00:00:00) - How do maternal histone methyltransferases regulate DNA health?(00:05:14) - The epigenetic tug of war in the worm(00:09:11) - Maternal DNA silencing(00:14:27) - Half the Story