Epigenetic regulation is important for establishing lineage-specific gene expression during early development. Although signaling pathways have been well-studied for regulation of trophectoderm reprogramming, epigenetic regulation of trophectodermal genes with histone modification dynamics have been poorly understood. Here, we identify that plant homeodomain finger protein 6 (PHF6) is a key epigenetic regulator for activation of trophectodermal genes using RNA-sequencing and ChIP assays. PHF6 acts as an E3 ubiquitin ligase for ubiquitination of H2BK120 (H2BK120ub) via its extended plant homeodomain 1 (PHD1), while the extended PHD2 of PHF6 recognizes acetylation of H2BK12 (H2BK12Ac). Intriguingly, the recognition of H2BK12Ac by PHF6 is important for exerting its E3 ubiquitin ligase activity for H2BK120ub. Together, our data provide evidence that PHF6 is crucial for epigenetic regulation of trophectodermal gene expression by linking H2BK12Ac to H2BK120ub modification.

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Current metagenomic classifiers analyze either DNA or amino-acid (AA) sequences. DNA-based methods have better specificity in distinguishing well-studied clades, but they have limited sensitivity in detecting under-studied clades. AA-based methods suffer the opposite problem. To tackle this trade-off, we developed Metabuli for a joint analysis of DNA and AA using a novel k-mer, metamer. In benchmarks, Metabuli was simultaneously as specific as DNA-based methods and as sensitive as AA-based methods. In the CAMI2 plant-associated dataset, Metabuli covers 99% and 98% of classifications of state-of-the-art DNA-based and AA-based classifiers, respectively. Metabuli is available as free and open-source software for Linux and macOS at metabuli.steineggerlab.com.

Current metagenomic classifiers analyze either DNA or amino-acid (AA) sequences. DNA-based methods have better specificity in distinguishing well-studied clades, but they have limited sensitivity in detecting under-studied clades. AA-based methods suffer the opposite problem. To tackle this trade-off, we developed Metabuli for a joint analysis of DNA and AA using a novel k-mer, metamer. In benchmarks, Metabuli was simultaneously as specific as DNA-based methods and as sensitive as AA-based methods. In the CAMI2 plant-associated dataset, Metabuli covers 99% and 98% of classifications of state-of-the-art DNA-based and AA-based classifiers, respectively. Metabuli is available as free and open-source software for Linux and macOS at metabuli.steineggerlab.com.