Granata J et al., PNAS - In mESCs and defined in vitro assays, EPOP and MTF2 stimulate PRC2 methyltransferase activity and promote de novo H3K27me3 deposition with GA- or GCN-rich DNA preference.

Study Highlights:
The study used mouse embryonic stem cells with an EED-rescue system and recombinant in vitro assays including HMT assays, EMSA, and ChIP-seq to probe EPOP and MTF2 function. Biochemical HMT assays on oligonucleosomes and dinucleosomes show both EPOP and MTF2 directly stimulate PRC2 catalytic activity, with MTF2 preferentially enhancing activity and binding on GCN-rich linkers and EPOP on GA-rich linkers. ChIP-seq during EED rescue demonstrated that EPOP is dispensable for initial PRC2 recruitment but its knockout reduces de novo H3K27me3 deposition by ~50% and cooperates with MTF2 and JARID2. Together these data indicate linker DNA sequence within nucleation sites guides subcomplex-specific PRC2 binding and catalytic output, influencing spatial establishment of H3K27me3 domains.

Conclusion:
EPOP and MTF2 define distinct PRC2 subcomplexes that stimulate PRC2 catalytic activity in a chromatin-dependent, DNA-sequence-specific manner to direct de novo H3K27me3 deposition.

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Reference:
Granata J., Liu S., Popoca L., Oksuz O., Reinberg D. EPOP and MTF2 activate PRC2 activity through DNA-sequence specificity. Proc. Natl. Acad. Sci. U.S.A. 2026;123:e2527303123. https://doi.org/10.1073/pnas.2527303123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.castos.com/episodes/epop-mtf2-prc2-sequence

Larsen BB et al., PNAS - Deep mutational scanning of the Nipah virus fusion protein F using pseudoviruses maps ~8,500 single-residue effects, showing F is highly constrained and identifying antibody-escape mutations.

Study Highlights:
Using nonreplicative lentiviral pseudoviruses and deep mutational scanning, the authors measured the effects of 8,449 single amino-acid mutations to the Nipah virus F ectodomain on cell entry in CHO cells expressing bat ephrin-B3. Measurements were fit with global epistasis models and mapped onto prefusion and postfusion structures, revealing the fusion peptide, lateral surface patches, and hexameric-interface residues are highly constrained. The library was screened against six monoclonal antibodies, quantifying mutation-mediated decreases in neutralization and showing distinct resilience among antibodies; specific Hendra F residues (Q70K, R336K) explained loss or reduction of neutralization by 4H3 and 1A9. The data nominate candidate proline substitutions and other sites for prefusion stabilization and inform vaccine and therapeutic antibody selection.

Conclusion:
Nipah virus F is highly functionally constrained relative to RBP with specific surface-exposed and core residues critical for cell entry, and antibody neutralization varies by epitope, informing prefusion-stabilized immunogen and therapeutic antibody design.

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Reference:
Larsen BB, Harari S, Gen R, Stewart C, Veesler D, Bloom JD. Functional and antigenic constraints on the Nipah virus fusion protein. Proc. Natl. Acad. Sci. U.S.A. 2026;123:e2529505123. https://doi.org/10.1073/pnas.2529505123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.castos.com/episodes/nipah-f-deep-mutational-map

Berazategui MA et al., PNAS - ESBX (Tb927.3.1660) links RNA Pol I localization at the ESB to activation of the active BES and repression of inactive BESs in Trypanosoma brucei, supporting monoallelic VSG expression.

Study Highlights:
Using ESB1-guided proximity-dependent biotinylation proteomics, endogenous tagging and high-resolution fluorescence microscopy, RNAi knockdown, RNA-seq, and inducible overexpression in bloodstream-form Trypanosoma brucei, the authors identify Tb927.3.1660 (ESBX) as an ESB-specific protein. ESBX localizes adjacent to Pol I (RPA2) and ESB1 within the ESB with measured center separations of ~68–175 nm and contains predicted SUMO-interacting and BRCT domains. ESBX depletion causes loss of the extranucleolar Pol I ESB focus, reduced processive transcription from the active BES with larger decreases distal to the promoter, and derepression of inactive BESs with low-processivity transcripts, whereas ESBX overexpression weakly activates inactive BESs with processive transcription without forming extra ESBs. Together the data indicate ESBX integrates activation of the active BES with repression of inactive BESs, a mechanism that supports monoallelic VSG expression.

Conclusion:
Tb927.3.1660/ESBX is an ESB component required to integrate activation of the active BES with repression of inactive BESs, thereby supporting monoallelic VSG expression in bloodstream-form Trypanosoma brucei.

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Reference:
Berazategui MA, Wheeler RJ, Tiengwe C, Lansink LIM, Rudenko G, Sunter JD, Goodwin I, Gull K, Faria JRC, et al. A factor integrating transcription and repression of surface antigen genes in African trypanosomes. Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2531377123. https://doi.org/10.1073/pnas.2531377123

License:
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Episode link: https://basebybase.castos.com/episodes/esbx-esb-vsg-regulation