Genes & development最新文献_第6页

Aging and immunity: the age-old tango 衰老与免疫：古老的探戈

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-28 DOI: 10.1101/gad.352644.125

Inés Fernández Maestre, Alexander S. Harris, Corina Amor

引用次数: 0

Bystander activation across a TAD boundary supports a cohesin-dependent transcription cluster model for enhancer function 跨TAD边界的旁观者激活支持增强子功能的内聚蛋白依赖转录簇模型

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-28 DOI: 10.1101/gad.352648.125

Iain Williamson, Katy A. Graham, Matthew Woolf, Hannes Becher, Robert E. Hill, Wendy A. Bickmore, Laura A. Lettice

{"title":"Bystander activation across a TAD boundary supports a cohesin-dependent transcription cluster model for enhancer function","authors":"Iain Williamson, Katy A. Graham, Matthew Woolf, Hannes Becher, Robert E. Hill, Wendy A. Bickmore, Laura A. Lettice","doi":"10.1101/gad.352648.125","DOIUrl":"https://doi.org/10.1101/gad.352648.125","url":null,"abstract":"Mammalian enhancers can regulate genes over large genomic distances, often skipping over other genes. Despite this, precise developmental regulation suggests that mechanisms exist to ensure enhancers only activate their correct targets. Sculpting of three-dimensional chromosome organization through cohesin-dependent loop extrusion is thought to be important for facilitating and constraining enhancer action. The boundaries of topologically associating domains (TADs) are thought to prevent enhancers acting on genes in adjacent TADs. However, there are examples where enhancers appear to act across TAD boundaries, but it has remained unclear whether a single enhancer can simultaneously activate genes in different TADs. Here we show that some Shh enhancers can activate transcription concurrently not only at Shh but also at Mnx1 located in an adjacent TAD. This occurs in the context of a chromatin conformation maintaining genes and enhancers in close proximity and is influenced by cohesin. To our knowledge, this is the first report of two endogenous mammalian genes transcribed concurrently under the control of the same enhancer and across a TAD boundary. These findings have implications for understanding the design rules of gene regulatory landscapes and are consistent with a transcription cluster model of enhancer–promoter communication.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"19 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164775","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

Epigenetic priming of neural progenitors by Notch enhances Sonic hedgehog signaling and establishes gliogenic competence Notch的表观遗传启动神经祖细胞增强Sonic hedgehog信号传导并建立胶质细胞生成能力

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-22 DOI: 10.1101/gad.352555.124

Luuli N. Tran, Ashwini Shinde, Kristen H. Schuster, Aiman Sabaawy, Emily Dale, Madalynn J. Welch, Trevor J. Isner, Sylvia A. Nunez, Fernando García-Moreno, Charles G. Sagerström, Bruce H. Appel, Santos J. Franco

{"title":"Epigenetic priming of neural progenitors by Notch enhances Sonic hedgehog signaling and establishes gliogenic competence","authors":"Luuli N. Tran, Ashwini Shinde, Kristen H. Schuster, Aiman Sabaawy, Emily Dale, Madalynn J. Welch, Trevor J. Isner, Sylvia A. Nunez, Fernando García-Moreno, Charles G. Sagerström, Bruce H. Appel, Santos J. Franco","doi":"10.1101/gad.352555.124","DOIUrl":"https://doi.org/10.1101/gad.352555.124","url":null,"abstract":"The remarkable cell diversity of multicellular organisms relies on the ability of multipotent progenitor cells to generate distinct cell types at the right times and locations during embryogenesis. A key question is how progenitors establish competence to respond to the different environmental signals required to produce specific cell types at critical developmental time points. We addressed this in the mouse developing forebrain, where neural progenitor cells must switch from producing neurons to making oligodendrocytes in response to increased Sonic hedgehog (SHH) signaling during late embryogenesis. We show that progenitor responses to SHH are regulated by Notch signaling, thus permitting proper timing of the neuron–oligodendrocyte switch. Notch activity epigenetically primes genes associated with the oligodendrocyte lineage and SHH pathway, enabling amplified transcriptional responses to endogenous SHH and robust oligodendrogenesis. These results reveal a critical role for Notch in facilitating progenitor competence states and influencing cell fate transitions at the epigenetic level.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"133 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123067","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

Restrictor slows RNAPII elongation to promote termination at noncoding RNA loci 限制子减缓RNAPII的延伸，促进在非编码RNA位点的终止

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-20 DOI: 10.1101/gad.352654.125

Claudia A. Mimoso, Hanneke Vlaming, Nathalie P. de Wagenaar, Allison P. Siegenfeld, Karen Adelman

{"title":"Restrictor slows RNAPII elongation to promote termination at noncoding RNA loci","authors":"Claudia A. Mimoso, Hanneke Vlaming, Nathalie P. de Wagenaar, Allison P. Siegenfeld, Karen Adelman","doi":"10.1101/gad.352654.125","DOIUrl":"https://doi.org/10.1101/gad.352654.125","url":null,"abstract":"The eukaryotic genome is broadly transcribed by RNA polymerase II (RNAPII) to produce protein-coding messenger RNAs (mRNAs) and a repertoire of noncoding RNAs (ncRNAs). Although RNAPII is very processive during mRNA transcription, it terminates rapidly during synthesis of many ncRNAs, particularly those that arise opportunistically from accessible chromatin at gene promoters or enhancers. The divergent fates of mRNA versus ncRNA species raise many questions about how RNAPII and associated machineries discriminate functional from spurious transcription. Restrictor, comprised of the RNA binding protein ZC3H4 and RNAPII-interacting protein WDR82, has been implicated in restraining the expression of ncRNAs. However, the determinants of Restrictor specificity and the mechanism of transcription suppression remain unclear. Here, we investigate Restrictor using unbiased sequence screens and rapid protein degradation followed by nascent RNA sequencing. We found that Restrictor promiscuously suppresses early elongation by RNAPII, but this activity is blocked at most mRNAs by the presence of a 5′ splice site. Consequently, Restrictor is a critical determinant of transcription directionality at divergent promoters and prevents transcriptional interference. Mechanistically, we show that rather than terminating RNAPII directly, Restrictor acts by reducing the rate of transcription elongation, rendering RNAPII susceptible to early termination by other machineries.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"55 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104615","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 mechanisms and neural mediators of leptin action 瘦素作用的分子机制和神经介质

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-20 DOI: 10.1101/gad.352550.124

Cagri Bodur, Allison Duensing, Martin G. Myers

{"title":"Molecular mechanisms and neural mediators of leptin action","authors":"Cagri Bodur, Allison Duensing, Martin G. Myers","doi":"10.1101/gad.352550.124","DOIUrl":"https://doi.org/10.1101/gad.352550.124","url":null,"abstract":"The adipose-derived hormone leptin signals the adequacy of body triglyceride stores to specialized leptin receptor (LepRb)-containing cells, which modulate physiology and behavior appropriately for the status of energy reserves. Decreased leptin action initiates a program that restrains a host of energy-intensive processes, promotes food seeking and consumption, and supports the continued availability of glucose and other metabolic fuels in the face of diminished fat stores. In addition to activating the STAT3-dependent transcriptional regulation that mediates most leptin action in vivo, LepRb mediates some leptin effects via a poorly understood second intracellular signaling pathway. Leptin also activates feedback pathways that restrain LepRb signaling in the face of high leptin, as in obesity. Leptin mediates most of its metabolic effects via multiple populations of Lepr-expressing hypothalamic neurons, each of which controls different aspects of leptin action. Although most of these neuron populations contribute only modestly to the control of food intake and body weight by leptin, Glp1r-expressing Lepr neurons inhibit Agrp neurons and strongly suppress feeding and body weight. Going forward, it will be important to define the potentially distinct intracellular responses to leptin for individual Lepr neuron populations, along with the cell type-specific roles for these responses in the physiologic effects of leptin.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"2 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104628","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

ETS emerges to heat up adipose ETS的出现是为了加热脂肪

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-19 DOI: 10.1101/gad.352966.125

Matthew S. Rodeheffer

引用次数: 0

TEAD switches interacting partners along neural progenitor lineage progression to execute distinct functions TEAD沿着神经祖谱系的进展切换相互作用的伙伴来执行不同的功能

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-19 DOI: 10.1101/gad.352632.125

Charles H. Perry, Alfonso Lavado, Venkata Thulabandu, Cody Ramirez, Joshua Paré, Rajiv Dixit, Akhilesh Mishra, Jiyuan Yang, Jiyang Yu, Xinwei Cao

{"title":"TEAD switches interacting partners along neural progenitor lineage progression to execute distinct functions","authors":"Charles H. Perry, Alfonso Lavado, Venkata Thulabandu, Cody Ramirez, Joshua Paré, Rajiv Dixit, Akhilesh Mishra, Jiyuan Yang, Jiyang Yu, Xinwei Cao","doi":"10.1101/gad.352632.125","DOIUrl":"https://doi.org/10.1101/gad.352632.125","url":null,"abstract":"The TEAD family of transcription factors is best known as the DNA-binding factor in the Hippo pathway, where these factors act by interacting with transcriptional coactivators YAP and TAZ (YAP/TAZ). Despite the importance of the Hippo pathway, the in vivo functions of TEAD in mammals have not been well established. By comparing mouse mutants lacking TEAD1 and TEAD2 (TEAD1/2) with those lacking YAP/TAZ, we found that TEAD1/2 have both YAP/TAZ-dependent and YAP/TAZ-independent functions during ventral telencephalon development. TEAD1/2 loss and YAP/TAZ loss similarly disrupt neuroepithelial apical junctions. However, the impacts of their losses on progenitor lineage progression are essentially opposite: YAP/TAZ loss depletes early progenitors and increases later progenitors, consistent with their established function in promoting progenitor self-renewal and proliferation, whereas TEAD1/2 loss expands early progenitors and reduces late progenitors, indicating that TEAD1/2 promote lineage progression. We further show that TEAD1/2 promote neural progenitor lineage progression by at least in part inhibiting Notch signaling and by cooperating with insulinoma-associated 1 (INSM1). Orthologs of TEAD and INSM1 have been shown to cooperatively regulate neuronal cell fate decisions in worms and flies. Our study reveals a remarkable evolutionary conservation of the function of this transcription factor complex during metazoan neural development.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"4 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097510","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

Ribosome association inhibits stress-induced gene mRNA localization to stress granules 核糖体结合抑制应激诱导基因mRNA向应激颗粒的定位

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-13 DOI: 10.1101/gad.352899.125

Noah S. Helton, Benjamin Dodd, Stephanie L. Moon

引用次数: 0

Cohesin in 3D: development, differentiation, and disease 三维内聚蛋白：发育、分化和疾病

IF 10.5 1区生物学

Genes & development Pub Date : 2025-05-09 DOI: 10.1101/gad.352671.125

Maria Solé-Ferran, Ana Losada

引用次数: 0

Drosha: a new tumor suppressor in pineoblastoma 一种新的松果体母细胞瘤抑制因子