Genes & development最新文献

mTORC1, the maestro of cell metabolism and growth mTORC1，细胞新陈代谢和生长的大师

IF 10.5 1区生物学

Genes & development Pub Date : 2024-11-21 DOI: 10.1101/gad.352084.124

Long He, Sungyun Cho, John Blenis

引用次数: 0

Proteomic insights into circadian transcription regulation: novel E-box interactors revealed by proximity labeling 蛋白质组学对昼夜节律转录调控的启示：通过邻近标记揭示新型 E-框相互作用子

IF 10.5 1区生物学

Genes & development Pub Date : 2024-11-19 DOI: 10.1101/gad.351836.124

Manon Torres, Marieluise Kirchner, Caroline G. Marks, Philipp Mertins, Achim Kramer

{"title":"Proteomic insights into circadian transcription regulation: novel E-box interactors revealed by proximity labeling","authors":"Manon Torres, Marieluise Kirchner, Caroline G. Marks, Philipp Mertins, Achim Kramer","doi":"10.1101/gad.351836.124","DOIUrl":"https://doi.org/10.1101/gad.351836.124","url":null,"abstract":"Circadian clocks (∼24 h) are responsible for daily physiological, metabolic, and behavioral changes. Central to these oscillations is the regulation of gene transcription. Previous research has identified clock protein complexes that interact with the transcriptional machinery to orchestrate circadian transcription, but technological constraints have limited the identification of de novo proteins. Here we use a novel genomic locus-specific quantitative proteomics approach to provide a new perspective on time of day-dependent protein binding at a critical chromatin locus involved in circadian transcription: the E-box. Using proximity labeling proteomics at the E-box of the clock-controlled Dbp gene in mouse fibroblasts, we identified 69 proteins at this locus at the time of BMAL1 binding. This method successfully enriched BMAL1 as well as HDAC3 and HISTONE H2A.V/Z, known circadian regulators. New E-box proteins include the MINK1 kinase and the transporters XPO7 and APPL1, whose depletion in human U-2 OS cells results in disrupted circadian rhythms, suggesting a role in the circadian transcriptional machinery. Overall, our approach uncovers novel circadian modulators and provides a new strategy to obtain a complete temporal picture of circadian transcriptional regulation.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"170 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673942","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

Evidence for dual roles of histone H3 lysine 4 in antagonizing Polycomb group function and promoting target gene expression 组蛋白 H3 赖氨酸 4 在拮抗多聚酶群功能和促进目标基因表达方面发挥双重作用的证据

IF 10.5 1区生物学

Genes & development Pub Date : 2024-11-19 DOI: 10.1101/gad.352181.124

Cyril S. Anyetei-Anum, Mary P. Leatham-Jensen, Geoffrey C. Fox, B. Rutledge Smith, Venkat R. Chirasani, Krzysztof Krajewski, Brian D. Strahl, Jill M. Dowen, A. Gregory Matera, Robert J. Duronio, Daniel J. McKay

{"title":"Evidence for dual roles of histone H3 lysine 4 in antagonizing Polycomb group function and promoting target gene expression","authors":"Cyril S. Anyetei-Anum, Mary P. Leatham-Jensen, Geoffrey C. Fox, B. Rutledge Smith, Venkat R. Chirasani, Krzysztof Krajewski, Brian D. Strahl, Jill M. Dowen, A. Gregory Matera, Robert J. Duronio, Daniel J. McKay","doi":"10.1101/gad.352181.124","DOIUrl":"https://doi.org/10.1101/gad.352181.124","url":null,"abstract":"Tight control over cell identity gene expression is necessary for proper adult form and function. The opposing activities of Polycomb and trithorax complexes determine the on/off state of cell identity genes such as the Hox factors. Polycomb group complexes repress target genes, whereas trithorax group complexes are required for their expression. Although trithorax and its orthologs function as methyltransferases specific to histone H3 lysine 4 (H3K4), there is no direct evidence that H3K4 regulates Polycomb group target genes in vivo. Using histone gene replacement in Drosophila, we provide evidence of two key roles for replication-dependent histone H3.2K4 in Polycomb target gene control. First, we found that H3.2K4 mutants mimic H3.2K4me3 in antagonizing methyltransferase activity of the PRC2 Polycomb group complex. Second, we found that H3.2K4 is also required for proper activation of Polycomb targets. We conclude that H3.2K4 directly regulates Polycomb target gene expression.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"57 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673940","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

PROSER1 modulates DNA demethylation through dual mechanisms to prevent syndromic developmental malformations PROSER1 通过双重机制调节 DNA 去甲基化，预防综合发育畸形

IF 10.5 1区生物学

Genes & development Pub Date : 2024-11-19 DOI: 10.1101/gad.352176.124

Anna Fleming, Elena V. Knatko, Xiang Li, Ansgar Zoch, Zoe Heckhausen, Stephanie Stransky, Alejandro J. Brenes, Simone Sidoli, Petra Hajkova, Dónal O'Carroll, Kasper D. Rasmussen

引用次数: 0

Genetics and biology of pancreatic ductal adenocarcinoma 胰腺导管腺癌的遗传学和生物学特性

IF 10.5 1区生物学

Genes & development Pub Date : 2024-11-07 DOI: 10.1101/gad.351863.124

Haoqiang Ying, Alec C. Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A. DePinho

{"title":"Genetics and biology of pancreatic ductal adenocarcinoma","authors":"Haoqiang Ying, Alec C. Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A. DePinho","doi":"10.1101/gad.351863.124","DOIUrl":"https://doi.org/10.1101/gad.351863.124","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and stromal cells that sustains anabolic growth and suppresses tumor immunity. These conceptual advances have generated novel immunotherapy regimens, particularly cancer vaccines, which are now in clinical testing. We also highlight the advent of KRAS targeted therapy, a milestone advance that has transformed treatment paradigms and offers a platform for combined immunotherapy and targeted strategies. This review provides a perspective summarizing current scientific and therapeutic challenges as well as practice-changing opportunities for the PDAC field at this major inflection point.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"1 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597548","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

BRCA1 and BRCA2: from cancer susceptibility to synthetic lethality BRCA1 和 BRCA2：从癌症易感性到合成致死性

IF 10.5 1区生物学

Genes & development Pub Date : 2024-11-07 DOI: 10.1101/gad.352083.124

Anna Khalizieva, Sarah C. Moser, Peter Bouwman, Jos Jonkers

引用次数: 0

Classifying the molecular functions of transcription factors beyond activation and repression. 对转录因子的分子功能进行分类，而不仅仅是激活和抑制。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-11-06 DOI: 10.1101/gad.352340.124

Jinhong Dong, Michael J Guertin

引用次数: 0

Deciphering normal and cancer stem cell niches by spatial transcriptomics: opportunities and challenges. 通过空间转录组学解读正常和癌症干细胞龛位：机遇与挑战。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-11-04 DOI: 10.1101/gad.351956.124

Hirak Sarkar, Eunmi Lee, Sereno L Lopez-Darwin, Yibin Kang

{"title":"Deciphering normal and cancer stem cell niches by spatial transcriptomics: opportunities and challenges.","authors":"Hirak Sarkar, Eunmi Lee, Sereno L Lopez-Darwin, Yibin Kang","doi":"10.1101/gad.351956.124","DOIUrl":"https://doi.org/10.1101/gad.351956.124","url":null,"abstract":"Cancer stem cells (CSCs) often exhibit stem-like attributes that depend on an intricate stemness-promoting cellular ecosystem within their niche. The interplay between CSCs and their niche has been implicated in tumor heterogeneity and therapeutic resistance. Normal stem cells (NSCs) and CSCs share stemness features and common microenvironmental components, displaying significant phenotypic and functional plasticity. Investigating these properties across diverse organs during normal development and tumorigenesis is of paramount research interest and translational potential. Advancements in next-generation sequencing (NGS), single-cell transcriptomics, and spatial transcriptomics have ushered in a new era in cancer research, providing high-resolution and comprehensive molecular maps of diseased tissues. Various spatial technologies, with their unique ability to measure the location and molecular profile of a cell within tissue, have enabled studies on intratumoral architecture and cellular cross-talk within the specific niches. Moreover, delineation of spatial patterns for niche-specific properties such as hypoxia, glucose deprivation, and other microenvironmental remodeling are revealed through multilevel spatial sequencing. This tremendous progress in technology has also been paired with the advent of computational tools to mitigate technology-specific bottlenecks. Here we discuss how different spatial technologies are used to identify NSCs and CSCs, as well as their associated niches. Additionally, by exploring related public data sets, we review the current challenges in characterizing such niches, which are often hindered by technological limitations, and the computational solutions used to address them.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575831","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

DNA-directed termination of mammalian RNA polymerase II 哺乳动物 RNA 聚合酶 II 的 DNA 定向终止

IF 10.5 1区生物学

Genes & development Pub Date : 2024-11-04 DOI: 10.1101/gad.351978.124

Lee Davidson, Jérôme O. Rouvière, Rui Sousa-Luís, Takayuki Nojima, Nicholas J. Proudfoot, Torben Heick Jensen, Steven West

{"title":"DNA-directed termination of mammalian RNA polymerase II","authors":"Lee Davidson, Jérôme O. Rouvière, Rui Sousa-Luís, Takayuki Nojima, Nicholas J. Proudfoot, Torben Heick Jensen, Steven West","doi":"10.1101/gad.351978.124","DOIUrl":"https://doi.org/10.1101/gad.351978.124","url":null,"abstract":"The best-studied mechanism of eukaryotic RNA polymerase II (RNAPII) transcriptional termination involves polyadenylation site-directed cleavage of the nascent RNA. The RNAPII-associated cleavage product is then degraded by XRN2, dislodging RNAPII from the DNA template. In contrast, prokaryotic RNAP and eukaryotic RNAPIII often terminate directly at T-tracts in the coding DNA strand. Here, we demonstrate a similar and omnipresent capability for mammalian RNAPII. Importantly, this termination mechanism does not require upstream RNA cleavage. Accordingly, T-tract-dependent termination can take place when XRN2 cannot be engaged. We show that T-tracts can terminate snRNA transcription independently of RNA cleavage by the Integrator complex. Importantly, we found genome-wide termination at T-tracts in promoter-proximal regions but not within protein-coding gene bodies. XRN2-dependent termination dominates downstream from protein-coding genes, but the T-tract process is sometimes used. Overall, we demonstrate global DNA-directed attrition of RNAPII transcription, suggesting that RNAPs retain the potential to terminate over T-rich sequences throughout evolution.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"195 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574711","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

Molecular and cellular dynamics of squamous cell carcinomas across tissues 不同组织鳞状细胞癌的分子和细胞动态变化

IF 10.5 1区生物学

Genes & development Pub Date : 2024-10-25 DOI: 10.1101/gad.351990.124

Matthew R. Kudelka, Yonit Lavin, Siman Sun, Elaine Fuchs

引用次数: 0