Genes & development最新文献_第2页

Corrigendum: Maternal Eed knockout causes loss of H3K27me3 imprinting and random X inactivation in the extraembryonic cells 更正：母体Eed基因敲除导致胚胎外细胞中H3K27me3印记缺失和随机X失活

IF 10.5 1区生物学

Genes & development Pub Date : 2025-09-01 DOI: 10.1101/gad.353016.125

Azusa Inoue, Zhiyuan Chen, Qiangzong Yin, Yi Zhang

引用次数: 0

MEF2C controls segment-specific gene regulatory networks that direct heart tube morphogenesis MEF2C控制直接心管形态发生的片段特异性基因调控网络

IF 10.5 1区生物学

Genes & development Pub Date : 2025-08-29 DOI: 10.1101/gad.352889.125

Jonathon M. Muncie-Vasic, Tanvi Sinha, Alexander P. Clark, Emily F. Brower, Jeffrey J. Saucerman, Brian L. Black, Benoit G. Bruneau

{"title":"MEF2C controls segment-specific gene regulatory networks that direct heart tube morphogenesis","authors":"Jonathon M. Muncie-Vasic, Tanvi Sinha, Alexander P. Clark, Emily F. Brower, Jeffrey J. Saucerman, Brian L. Black, Benoit G. Bruneau","doi":"10.1101/gad.352889.125","DOIUrl":"https://doi.org/10.1101/gad.352889.125","url":null,"abstract":"The gene regulatory networks (GRNs) that control early heart formation are beginning to be understood, but lineage-specific GRNs remain largely undefined. We investigated networks controlled by the vital transcription factor MEF2C using a time course of single-nucleus RNA sequencing and ATAC sequencing in wild-type and Mef2c-null embryos. We identified a “posteriorized” cardiac gene signature and chromatin landscape in the absence of MEF2C. Integrating our multiomics data in a deep learning-based model, we constructed developmental trajectories for each of the outflow tract, ventricular, and inflow tract segments and alterations of these in Mef2c-null embryos. We computationally identified segment-specific MEF2C-dependent enhancers with activity in the developing zebrafish heart. Finally, using inferred GRNs, we discovered that the Mef2c-null heart malformations are partly driven by increased activity of the nuclear hormone receptor NR2F2. Our results delineate lineage-specific GRNs in the early heart tube and provide a generalizable framework for dissecting transcriptional networks governing developmental processes.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"23 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915581","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}

引用次数: 0

End of the line: a kinetic ruler model for poly(A) tail termination 终点线：poly(a)尾部终止的动力学尺子模型

IF 10.5 1区生物学

Genes & development Pub Date : 2025-08-26 DOI: 10.1101/gad.353241.125

Anita H. Corbett

引用次数: 0

UPR deficiency leads to poor growth, aneuploidy, and a trade-off between ER and general proteostasis in yeast UPR缺乏导致生长不良，非整倍性，以及ER和酵母中一般蛋白质停滞之间的权衡

IF 10.5 1区生物学

Genes & development Pub Date : 2025-08-22 DOI: 10.1101/gad.352490.124

Constantine Bartolutti, Allison J. Kim, Yanzhe Ma, Thiago P. Fernandes, Charles Boone, Marko Jovanovic, Gloria A. Brar

{"title":"UPR deficiency leads to poor growth, aneuploidy, and a trade-off between ER and general proteostasis in yeast","authors":"Constantine Bartolutti, Allison J. Kim, Yanzhe Ma, Thiago P. Fernandes, Charles Boone, Marko Jovanovic, Gloria A. Brar","doi":"10.1101/gad.352490.124","DOIUrl":"https://doi.org/10.1101/gad.352490.124","url":null,"abstract":"The unfolded protein response (UPR) was discovered in budding yeast as a mechanism that allows cells to adapt to endoplasmic reticulum (ER) stressors. Although the UPR is not thought to be necessary for cellular fitness of wild-type cells in the absence of stress, we found that UPR deficiency led to poor growth in cycling mitotic yeast cells. This led to pervasive adaptive aneuploidy of specific chromosomes that was seen in divergent strain backgrounds, indicating an important basal role for this pathway that was missed by studies of the most common laboratory-derived strains. Aneuploid UPR-deficient cells grew better than euploid UPR-deficient cells but exhibited heightened general proteostatic stress, a hallmark of aneuploidy in wild-type cells. Modulation of key genes involved in ER proteostasis that were encoded on aneuploid chromosomes could phenocopy the effects of aneuploidy, indicating that the reason UPR-deficient cells become aneuploid is to counteract protein folding stress in the ER. Proteomic analyses indicate that expression of a small subset of stress-induced UPR targets is supported by basal UPR activity, including the chaperone Kar2/BiP. Together, our results reveal an unexpected role for the UPR in baseline ER folding that is important enough to safeguard cellular fitness that cells tolerate the substantial proteostatic costs that result from aneuploidy to counteract its loss.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"17 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898386","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}

引用次数: 0

Dominant-negative effects of Weaver syndrome-associated EZH2 variants 韦弗综合征相关EZH2变异的显性负作用

IF 10.5 1区生物学

Genes & development Pub Date : 2025-08-22 DOI: 10.1101/gad.351884.124

Orla Deevy, Jingjing Li, Craig Monger, Francesca Matrà, Ellen Tuck, Molly Davies, Mihaly Badonyi, Maeve Boyce, Emma J. Doyle, Karsten Hokamp, Darragh Nimmo, Simona Rodighiero, Qi Zhang, Chen Davidovich, Joseph A. Marsh, Diego Pasini, Eric Conway, Adrian P. Bracken

{"title":"Dominant-negative effects of Weaver syndrome-associated EZH2 variants","authors":"Orla Deevy, Jingjing Li, Craig Monger, Francesca Matrà, Ellen Tuck, Molly Davies, Mihaly Badonyi, Maeve Boyce, Emma J. Doyle, Karsten Hokamp, Darragh Nimmo, Simona Rodighiero, Qi Zhang, Chen Davidovich, Joseph A. Marsh, Diego Pasini, Eric Conway, Adrian P. Bracken","doi":"10.1101/gad.351884.124","DOIUrl":"https://doi.org/10.1101/gad.351884.124","url":null,"abstract":"Heterozygous missense mutations in EZH2 cause Weaver syndrome (WS), a developmental disorder characterized by intellectual disability and overgrowth. EZH2 encodes the enzymatic subunit of Polycomb repressive complex 2 (PRC2), which mediates monomethylation, dimethylation, and trimethylation of histone H3 lysine 27 (H3K27me1/2/3). Most WS-associated EZH2 variants lack functional characterization but are presumed loss-of-function. However, the lack of early truncating mutations in EZH2 led us to hypothesize a dominant-negative mechanism for WS, which was supported by our structural analysis of all known WS-associated EZH2 variants. We isogenically modeled 10 representative variants in embryonic stem cells and showed that they reduce global H3K27me2/3 with concomitant increases in H3K27ac and chromatin decompaction. Notably, the pattern of H3K27me2/3 reductions indicated dominant-negative interference on PRC2 activity even when WS variants were expressed at low levels. RNA-seq identified weakly Polycomb-bound genes that lose canonical PRC1 (cPRC1) occupancy and become derepressed, including several phenotypically relevant growth control genes. Comparative analysis of a gain-of-function EZH2 variant causing growth restriction revealed reciprocal chromatin and transcriptional changes compared with WS-associated variants. Taken together, our findings support a model in which EZH2 variants associated with opposing developmental growth syndromes affect not only H3K27me3 but also intergenic H3K27me2, chromatin architecture, and cPRC1 recruitment.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"26 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898388","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}

引用次数: 0

A kinetic ruler controls mRNA poly(A) tail length 一个动力学尺子控制mRNA poly(A)尾巴长度

IF 10.5 1区生物学

Genes & development Pub Date : 2025-08-22 DOI: 10.1101/gad.352912.125

Emilie Gabs, Emil Aalto-Setälä, Aada Välisaari, Anssi M. Malinen, Torben Heick Jensen, Stephen H. McLaughlin, Lori A. Passmore, Matti Turtola

{"title":"A kinetic ruler controls mRNA poly(A) tail length","authors":"Emilie Gabs, Emil Aalto-Setälä, Aada Välisaari, Anssi M. Malinen, Torben Heick Jensen, Stephen H. McLaughlin, Lori A. Passmore, Matti Turtola","doi":"10.1101/gad.352912.125","DOIUrl":"https://doi.org/10.1101/gad.352912.125","url":null,"abstract":"Poly(A) tails of newly synthesized mRNAs have uniform lengths, arising through cooperation between the cleavage and polyadenylation complex (CPAC) and poly(A) binding proteins (PABPs). In the budding yeast Saccharomyces cerevisiae, the responsible PABP is the evolutionarily conserved CCCH zinc finger protein Nab2 that facilitates the biogenesis of ∼60 adenosine mRNA poly(A) tails. Here, we address the molecular basis for such length control. Reconstituting polyadenylation reactions during the formation of Nab2:poly(A) RNA ribonucleoprotein particles in vitro, we found that Nab2 dimerization directs polyadenylation termination. The Nab2 dimer is stable only on poly(A) tails that are >25 adenosines, explaining how Nab2 avoids prematurely terminating poly(A) synthesis. However, the mature tail length is not determined by the footprint of Nab2 on the RNA but rather by the kinetic competition between CPAC-mediated tail elongation and Nab2 RNA binding. Variations in Nab2 RNA binding rate can shift poly(A) tail lengths, but in cells such variations are buffered by autoregulation of Nab2 protein concentration. As a result, poly(A) tail length control operates through a “kinetic ruler” mechanism, whereby the concentration of Nab2 quantifies RNA length.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"43 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898432","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}

引用次数: 0

Multifaceted role of the vitamin B6 pathway in cancer: metabolism, immune interaction, and temporal and spatial regulation 维生素B6通路在癌症中的多重作用：代谢、免疫相互作用和时空调节

IF 10.5 1区生物学

Genes & development Pub Date : 2025-08-22 DOI: 10.1101/gad.352770.125

Sushanta Kumar Mishra, Bo Li, Ana S.H. Costa, Linda Van Aelst, Lingbo Zhang

引用次数: 0

H3K4me3 amplifies transcription at intergenic active regulatory elements. H3K4me3扩增基因间活性调控元件的转录。

IF 7.7 1区生物学

Genes & development Pub Date : 2025-08-18 DOI: 10.1101/gad.352841.125

Haoming Yu, Yongyan Zhang, Zhicong Liao, Benjamin William Walters, Bluma J Lesch

引用次数: 0

A new link in the leukemia genetic puzzle 白血病基因之谜的新线索

IF 10.5 1区生物学

Genes & development Pub Date : 2025-08-12 DOI: 10.1101/gad.353189.125

Xiaodi Wu, Ross L. Levine

引用次数: 0

Mouse cortical cellular diversification through lineage progression of radial glia. 小鼠皮层细胞分化通过放射状胶质细胞的谱系进展。

IF 7.7 1区生物学

Genes & development Pub Date : 2025-08-07 DOI: 10.1101/gad.352826.125

Lin Yang, Ziwu Wang, Yanjing Gao, Zhenmeiyu Li, Guoping Liu, Zhejun Xu, Zhuangzhi Zhang, Yan You, Zhengang Yang, Xiaosu Li

{"title":"Mouse cortical cellular diversification through lineage progression of radial glia.","authors":"Lin Yang, Ziwu Wang, Yanjing Gao, Zhenmeiyu Li, Guoping Liu, Zhejun Xu, Zhuangzhi Zhang, Yan You, Zhengang Yang, Xiaosu Li","doi":"10.1101/gad.352826.125","DOIUrl":"https://doi.org/10.1101/gad.352826.125","url":null,"abstract":"Cortical radial glia (RGs) sequentially generate pyramidal neurons (PyNs) and glia. In this study, we investigated the cell-intrinsic programs underlying cortical cellular diversification using time-series scRNA-seq and snATAC-seq on purified mouse cortical progenitors across embryonic and postnatal stages. Our data revealed that RGs transition from early to late over time, sequentially producing intermediate neuronal progenitors (INPs) and intermediate glial progenitors (IGPs). Although INPs expand exclusively to generate PyNs, IGPs progress from young to old, sequentially producing cortical astrocytes, oligodendrocytes, and olfactory bulb interneurons. We constructed comprehensive molecular maps that reflect cell lineage progression. In particular, we found that chromatin accessibility drives cortical cellular diversification by restricting broadly expressed transcription factors to specific stages and cell types. Developmental changes in chromatin accessibility confine Lhx2-induced neurogenesis to early-stage RGs, leading to the loss of neurogenic competence and the acquisition of gliogenic competence as corticogenesis progresses.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798822","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}

引用次数: 0