Thomas Willott, James G Nicholson, Xinyu Zhang, Yunchen Xiao, Olumide Ogunbiyi, Benjamin Draper, Talisa Mistry, Laura K Donovan, Ashirwad Merve, Nicolae Radu Zabet, Sara Badodi, Silvia Marino
{"title":"Modeling medulloblastoma pathogenesis and treatment in human cerebellar organoids.","authors":"Thomas Willott, James G Nicholson, Xinyu Zhang, Yunchen Xiao, Olumide Ogunbiyi, Benjamin Draper, Talisa Mistry, Laura K Donovan, Ashirwad Merve, Nicolae Radu Zabet, Sara Badodi, Silvia Marino","doi":"10.1101/gad.353292.125","DOIUrl":"10.1101/gad.353292.125","url":null,"abstract":"<p><p>Medulloblastoma (MB) groups 3 and 4 arise from human-specific developmental contexts that remain experimentally inaccessible, limiting mechanistic insight into tumor initiation. We generated cerebellar organoids (CbOs) from expanded potential stem cells (EPSCs) and performed integrated single-cell transcriptomic and DNA methylation analyses, revealing discrete human rhombic lip progenitor populations whose developmental programs align with group 3- and group 4-associated lineages. Using c-<i>MYC</i> overexpression as an initiating oncogenic event, we demonstrated that these lineage-restricted progenitors are susceptible to neoplastic transformation, generating tumors with group 3 MB molecular features in vitro and in vivo. We further established a CbO-MB coculture system that preserves malignant and nonmalignant cellular compartments, hence enabling interrogation of tumor-microenvironment interactions and providing simultaneous readouts of antitumor efficacy and cerebellar toxicity upon drug treatment. Receptor-ligand modeling in this system identifies TGFβ paracrine signaling as a microenvironmental pathway supporting MB growth, which we validated pharmacologically. Further analyses of cocultured MB cells revealed a myogenic differentiation program enriched in <i>MYC</i>-driven MB and recurrent disease, which is associated with poorer prognosis. Together, this work establishes a collection of CbO models for studying group 3/4 MB initiation, growth, and microenvironmental dependencies and provides a tractable platform for further mechanistic and therapeutic investigation of these tumors.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"936-955"},"PeriodicalIF":7.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147768976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Moreno Martinovic, Koen D Flach, Marit A C de Kort, Michela Maresca, Hans Teunissen, Ning Qing Liu, Tineke L Lenstra, Elzo de Wit
{"title":"Cohesin-mediated loop extrusion and enhancer-associated factors additively contribute to <i>Sox2</i> looping with its distal enhancer.","authors":"Moreno Martinovic, Koen D Flach, Marit A C de Kort, Michela Maresca, Hans Teunissen, Ning Qing Liu, Tineke L Lenstra, Elzo de Wit","doi":"10.1101/gad.353296.125","DOIUrl":"10.1101/gad.353296.125","url":null,"abstract":"<p><p><i>Sox2</i> expression is regulated by a distal enhancer cluster known as the <i>Sox2</i> control region (SCR). Although <i>Sox2</i> and the SCR exhibit strong interactions in chromosome conformation capture experiments, acute depletion of cohesin only mildly affects <i>Sox2</i> transcription. Here we show that continuous restarting of loop extrusion, but not stalling of cohesin at CTCF sites, is involved in the maintenance of the <i>Sox2</i>-SCR loop. While depletion of cohesin or CTCF has only a mild impact on <i>Sox2</i> gene expression, stabilizing cohesin on the DNA by depleting the cohesin release factor WAPL results in a rapid decrease in expression. Furthermore, using genome editing, we show that a weak enhancer located downstream from the <i>Sox2</i> gene renders <i>Sox2</i> expression insensitive to the loss of cohesin stalling at CTCF sites. Finally, through targeted and pleiotropic inhibition of the SCR, we demonstrate that the <i>Sox2</i>-SCR loop is a multicomponent system that depends on cohesin-mediated loop extrusion and enhancer-associated factors. Together, our findings highlight the intricate interplay between enhancer activity and loop extrusion in the establishment and maintenance of chromatin loops in the <i>Sox2</i> locus.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"893-911"},"PeriodicalIF":7.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glc7/PP1 triggers Paf1 complex dissociation from RNA polymerase II to enable transcription termination.","authors":"Sanchirmaa Namjilsuren, Karen M Arndt","doi":"10.1101/gad.353379.125","DOIUrl":"10.1101/gad.353379.125","url":null,"abstract":"<p><p>The mechanisms that control the dynamic composition of RNAPII elongation complexes govern major transitions in the transcription cycle yet are poorly understood. Here, we show that the transcription elongation factor Spt5 determines elongation complex composition to promote productive elongation and the transition to termination. Using an unbiased genetic screen and genomic approaches in <i>Saccharomyces cerevisiae</i>, we provide evidence that dephosphorylation of the Spt5 C-terminal repeat domain (CTR) by Glc7/PP1 is required to dislodge the Paf1 complex (Paf1C) from RNAPII near the cleavage and polyadenylation site (CPS). Mutations in Paf1C or the Spt5 CTR that dissociate Paf1C from RNAPII bypass the requirement for two critical regulators of Glc7 in the cleavage and polyadenylation factor that promote Glc7 enrichment at the 3' ends of genes. Depletion of Glc7 causes aberrant retention of Paf1C past the CPS and a dramatic increase in readthrough transcription, which is fully suppressed by Paf1C mutations. Our results demonstrate that Paf1C retention antagonizes transcription termination and that Glc7-mediated restructuring of the RNAPII elongation complex to evict Paf1C at the CPS is a critical step in the transition from elongation to termination.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"699-716"},"PeriodicalIF":7.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enquan Xu, Christina Zhang, Fausto J Rodriguez, Sonika Dahiya, Corina Anastasaki, David H Gutmann
{"title":"Nested pediatric low-grade glioma cerebral organoid avatars reveal glutamatergic neuron stromal growth dependency.","authors":"Enquan Xu, Christina Zhang, Fausto J Rodriguez, Sonika Dahiya, Corina Anastasaki, David H Gutmann","doi":"10.1101/gad.353336.125","DOIUrl":"10.1101/gad.353336.125","url":null,"abstract":"<p><p>Pilocytic astrocytomas (PAs), the most common pediatric brain tumor, grow slowly and depend heavily on their local brain microenvironment, hindering accurate humanized model development. To surmount this barrier, we developed mixed assembloids of PAs nested within human iPSC-cerebral organoids (PANCOs) that recapitulate PA histopathology and growth. Consistent with their cell-intrinsic ERK dependence, MEK inhibition reduces PANCO proliferation, whereas clozapine-N-oxide-activatable neural progenitors integrate into PANCOs, preferentially differentiate into glutamatergic neurons, and increase cell-extrinsic PA proliferation, which is blocked by glutamate receptor inhibition. These accurate in vitro pediatric PA avatars provide tractable platforms to discover and validate PA cell-intrinsic and cell-extrinsic growth dependencies.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"638-649"},"PeriodicalIF":7.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lights up on the embryonic dance: tools and applications of optogenetics in developmental biology.","authors":"Yang Gao, Emily K Ho, Jared E Toettcher","doi":"10.1101/gad.353459.125","DOIUrl":"10.1101/gad.353459.125","url":null,"abstract":"<p><p>In developmental biology, cellular events must be orchestrated at precise times and locations in the embryo. Many classic discoveries were achieved by perturbing developmental organization using approaches ranging from tissue transplantation to local, acute heat shock. A growing suite of optogenetic tools is now available with fine spatiotemporal control, opening the door to perturbation experiments with unprecedented precision. Here we highlight these tools, review their application in developmental contexts, and discuss their current challenges and future promise.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"607-626"},"PeriodicalIF":7.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janith A Seneviratne, Clare L Crisp, Eleanor Glancy, Natalie Choy, Winnie Tan, Matthew Neve, Melanie Stammers, Tongtong Wang, Ruby Johnstone, Arshnoor Kaur, Katie A Fennell, Marian L Burr, Benjamin L Parker, Shabih Shakeel, Melanie A Eckersley-Maslin
{"title":"Embryonic stem cell factors DPPA2/4 amplify active H3K4me3-H2AK119ub chromatin domains in non-small cell lung cancer.","authors":"Janith A Seneviratne, Clare L Crisp, Eleanor Glancy, Natalie Choy, Winnie Tan, Matthew Neve, Melanie Stammers, Tongtong Wang, Ruby Johnstone, Arshnoor Kaur, Katie A Fennell, Marian L Burr, Benjamin L Parker, Shabih Shakeel, Melanie A Eckersley-Maslin","doi":"10.1101/gad.353102.125","DOIUrl":"10.1101/gad.353102.125","url":null,"abstract":"<p><p>Embryonic regulators are often re-expressed in cancers; however, the functional and molecular significance of this is not always understood. The epigenetic priming factors developmental pluripotency-associated 2 and 4 (DPPA2/4) have crucial roles in early development and are implicated in cancer pathogenesis. We reveal that in non-small cell lung cancer (NSCLC), DPPA2/4 coexpression is associated with poorly differentiated tumors and impaired patient outcomes. Biochemically, human DPPA2/4 multimerize for their protein stability and enhanced nucleosome binding activity. In NSCLC cells, DPPA2/4 bind CG-rich sequences including promoters of developmental genes, Wnt signaling, and catabolic genes. Chromatin state modeling revealed that DPPA2/4 preferentially bind active H3K4me3 and H3K27ac domains that were intriguingly also enriched for PRC1 and its product, H2AK119ub, which was validated by H3K4me3-H2AK119ub sequential ChIP. Knockdown experiments revealed that DPPA2/4 were required to maintain RING1B and H2AK119ub at these domains. Surprisingly, despite the presence of PRC2.1, these regions lacked any detectable H3K27me3, suggesting an uncoupling between the recruitment of PRC2 to chromatin and its catalytic product. When exogenously overexpressed in NSCLC cells where they are not normally present, DPPA2/4 bind to and promote active chromatin states, resulting in an increase in in vivo xenograft tumor growth. Our results demonstrate how, in NSCLC cells, DPPA2/4 act as molecular amplifiers of active and poised chromatin. Together, this highlights how aberrant reactivation of embryonic factors in cancers may take on new functions, promoting tumorigenesis.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"756-776"},"PeriodicalIF":7.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessa R Ringel, Natalia Benetti, Andreas Magg, Fabian Groll, Robert Schöpflin, Mira Kühnlein, Asita Carola Stiege, Ute Fischer, Lars Wittler, Laurence Game, Stephan Lorenz, George Young, Stefan Mundlos, Lila Allou
{"title":"Temporal loss of <i>En1</i> during limb development causes distinct phenotypes.","authors":"Alessa R Ringel, Natalia Benetti, Andreas Magg, Fabian Groll, Robert Schöpflin, Mira Kühnlein, Asita Carola Stiege, Ute Fischer, Lars Wittler, Laurence Game, Stephan Lorenz, George Young, Stefan Mundlos, Lila Allou","doi":"10.1101/gad.353542.125","DOIUrl":"10.1101/gad.353542.125","url":null,"abstract":"<p><p>The precise spatiotemporal regulation of developmental genes is required for proper organogenesis. <i>Engrailed-1</i> (<i>En1</i>) is essential for dorsal-ventral patterning during mouse limb development from embryonic day 9.5 (E9.5) to E11.5. Previously, we identified the long noncoding RNA locus <i>Maenli</i>, which drives limb-specific <i>En1</i> expression at E9.5. Here, we uncover two intergenic enhancer elements, <i>LSEE1</i>&<i>2</i>, that are essential for <i>En1</i> expression at E10.5 and E11.5. We demonstrate that <i>Maenli</i> and <i>LSEE1&2</i> coordinate two transcriptional waves of <i>En1</i> expression that are essential for establishing dorsal-ventral limb identity. The early wave, controlled by <i>Maenli</i>, is required for ventral ectoderm and apical ectodermal ridge specification, while the late wave, associated with <i>LSEE1&2</i>, is critical for dorsal-ventral ectoderm specification in mouse limbs. Loss of <i>Maenli</i> versus <i>LSEE1&2</i> results in distinct developmental phenotypes by altering the spatiotemporal expression of key genes governing axial patterning pathways. Our study underscores how temporal <i>cis</i>-regulatory elements modulate lineage specification and developmental patterning through shaping spatiotemporal gene function during development, representing potential candidates underpinning isolated subphenotypes.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"627-637"},"PeriodicalIF":7.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acadia L Grimme, Lu Li, Alyshia Scholl, Bridget F Donnelly, Neha Channamraju, Karl-Frédéric Vieux, Lecong Zhou, Geraldine Seydoux, Mingyi Xie, Katherine McJunkin
{"title":"A lncRNA drives developmentally timed decay of all members of an essential microRNA family.","authors":"Acadia L Grimme, Lu Li, Alyshia Scholl, Bridget F Donnelly, Neha Channamraju, Karl-Frédéric Vieux, Lecong Zhou, Geraldine Seydoux, Mingyi Xie, Katherine McJunkin","doi":"10.1101/gad.353314.125","DOIUrl":"10.1101/gad.353314.125","url":null,"abstract":"<p><p>The spatiotemporal expression patterns of microRNAs (miRNAs) are crucial to their function. Target-directed miRNA degradation (TDMD) is an emerging regulatory module that contributes to these expression patterns wherein a specialized RNA (a TDMD trigger) drives miRNA decay through base pairing and the resulting recruitment of E3 ubiquitin ligase ZSWIM8/EBAX-1. Extensive base pairing to the miRNA seed region and 3' end has been proposed as a key feature that distinguishes TDMD triggers from conventional mRNA targets of miRNAs, which primarily pair with the seed. Here we identify the long noncoding RNA <i>tts-2</i> as a TDMD trigger for <i>mir-35-42</i>, the most abundant miRNA family in <i>Caenorhabditis elegans</i> early embryos. We demonstrate that a single site in <i>tts-2</i> drives decay through base pairing with the seed sequence shared by all eight family members. A second site in <i>tts-2</i> supports decay of <i>mir-38</i> with incomplete seed complementarity. Retargeting <i>tts-2</i> to other miRNAs suggests that the GC-rich seed of <i>mir-35-42</i> allows for seed-sufficient TDMD. Our findings demonstrate that extended base pairing is not a universal requirement of TDMD and that TDMD drives developmentally timed clearance of abundant miRNAs at the exit of <i>C. elegans</i> embryogenesis.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"737-755"},"PeriodicalIF":7.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"α-Satellite RNA marks the perinucleolar compartment and represses ribosomal RNA expression in naive human embryonic stem cells.","authors":"Kirti Mittal, Lamisa Ataei, Miguel Ramalho-Santos","doi":"10.1101/gad.353162.125","DOIUrl":"10.1101/gad.353162.125","url":null,"abstract":"<p><p>While most newly synthesized RNA is exported to the cytoplasm, a portion of noncoding RNA is retained in the nucleus and remains highly associated with chromatin. The strong binding of this RNA fraction to insoluble chromatin impairs its recovery in standard transcriptomic studies. Therefore, the landscape and potential functions of chromatin-associated RNAs are poorly understood. Recent studies indicate that chromatin-associated transcripts can have regulatory roles, particularly during mammalian development. Here we compare the dynamics of cytoplasmic versus chromatin-bound transcriptomes of naive and primed human embryonic stem cells (hESCs) as well as fibroblasts. We found a remarkable enrichment for RNA transcribed from α-satellite repeat (ALR) in the chromatin fraction of naive hESCs compared with primed hESCs. The colocalization and interaction of ALR RNA with polypyrimidine tract binding protein 1 (PTBP1) and CUG-binding protein (CUGBP) indicate that ALR RNA foci mark the perinucleolar compartment (PNC), a nuclear subcompartment previously thought to be exclusive to cancer cells. Knockdown of ALR RNA leads to dispersion of PTBP1/CUGBP foci, upregulation of ribosomal RNA, and global hypertranscription in naive hESCs. In contrast, loss of PTBP1 does not disturb ALR RNA localization, indicating that ALR is upstream in the hierarchy of organization of the PNC in hESCs. These results reveal a role for ALR RNA in nuclear compartmentalization and tuning rRNA synthesis in naive hESCs. Moreover, this study opens new avenues to dissect the function of ALR RNA and the PNC in cancer contexts.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"717-736"},"PeriodicalIF":7.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agata L Patriotis, Douglas W Barrows, Yadira Soto-Feliciano, Laiba F Khan, Marylene Leboeuf, Dylan M Marchione, Matthew R Marunde, Michael-Christopher Keogh, Thomas S Carroll, Benjamin A Garcia, Alexey A Soshnev, C David Allis
{"title":"The conserved N-terminal SANT1-binding domain (SBD) of EZH2 regulates PRC2 activity.","authors":"Agata L Patriotis, Douglas W Barrows, Yadira Soto-Feliciano, Laiba F Khan, Marylene Leboeuf, Dylan M Marchione, Matthew R Marunde, Michael-Christopher Keogh, Thomas S Carroll, Benjamin A Garcia, Alexey A Soshnev, C David Allis","doi":"10.1101/gad.353070.125","DOIUrl":"10.1101/gad.353070.125","url":null,"abstract":"<p><p>Polycomb group proteins maintain gene expression patterns established during early development, with Polycomb repressive complex 2 (PRC2) methyltransferase being a key regulator of cell differentiation, identity, and plasticity. Consequently, extensive somatic mutations in PRC2, including gain or loss of function (GOF or LOF), are observed in human cancers. The regulation of chromatin structure by PRC2 is critically dependent on its enhancer of zeste homolog 2 (EZH2) subunit, which catalyzes the methylation of histone H3 lysine 27 (H3K27). Recent structural studies of PRC2 revealed extensive conformational changes in the noncatalytic EZH2 N-terminal SANT1-binding domain (SBD) during PRC2 activation, though the functional significance remains unclear. Here, we investigated how the SBD regulates PRC2 function. The domain is highly conserved in metazoans and dispensable for PRC2 assembly and chromatin localization yet is required for genome-wide histone H3K27 methylation. Furthermore, we show that an intact SBD is necessary for the proliferation of EZH2-addicted lymphomas, and its deletion in the presence of <i>EZH2</i> GOF mutations inhibits cancer cell growth. These observations provide new insights into the regulation of PRC2 activity in normal development and malignancy.</p>","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"650-665"},"PeriodicalIF":7.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}