Genes & development最新文献_第6页

Nuclear receptor signaling via NHR-49/MDT-15 regulates stress resilience and proteostasis in response to reproductive and metabolic cues. 核受体信号通过NHR-49/MDT-15调节应激复原力和蛋白稳态，以应对生殖和代谢线索。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-06-25 DOI: 10.1101/gad.351829.124

Ambre J Sala, Rogan A Grant, Ghania Imran, Claire Morton, Renee M Brielmann, Szymon Gorgoń, Jennifer Watts, Laura C Bott, Richard I Morimoto

{"title":"Nuclear receptor signaling via NHR-49/MDT-15 regulates stress resilience and proteostasis in response to reproductive and metabolic cues.","authors":"Ambre J Sala, Rogan A Grant, Ghania Imran, Claire Morton, Renee M Brielmann, Szymon Gorgoń, Jennifer Watts, Laura C Bott, Richard I Morimoto","doi":"10.1101/gad.351829.124","DOIUrl":"10.1101/gad.351829.124","url":null,"abstract":"The ability to sense and respond to proteotoxic insults declines with age, leaving cells vulnerable to chronic and acute stressors. Reproductive cues modulate this decline in cellular proteostasis to influence organismal stress resilience in Caenorhabditis elegans We previously uncovered a pathway that links the integrity of developing embryos to somatic health in reproductive adults. Here, we show that the nuclear receptor NHR-49, an ortholog of mammalian peroxisome proliferator-activated receptor α (PPARα), regulates stress resilience and proteostasis downstream from embryo integrity and other pathways that influence lipid homeostasis and upstream of HSF-1. Disruption of the vitelline layer of the embryo envelope, which activates a proteostasis-enhancing intertissue pathway in somatic cells, triggers changes in lipid catabolism gene expression that are accompanied by an increase in fat stores. NHR-49, together with its coactivator, MDT-15, contributes to this remodeling of lipid metabolism and is also important for the elevated stress resilience mediated by inhibition of the embryonic vitelline layer. Our findings indicate that NHR-49 also contributes to stress resilience in other pathways known to change lipid homeostasis, including reduced insulin-like signaling and fasting, and that increased NHR-49 activity is sufficient to improve proteostasis and stress resilience in an HSF-1-dependent manner. Together, our results establish NHR-49 as a key regulator that links lipid homeostasis and cellular resilience to proteotoxic stress.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"380-392"},"PeriodicalIF":7.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179474","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}

引用次数: 0

Diverse Fgfr1 signaling pathways and endocytic trafficking regulate mesoderm development. 多种Fgfr1信号通路和内细胞贩运调控中胚层发育

IF 7.5 1区生物学

Genes & development Pub Date : 2024-06-25 DOI: 10.1101/gad.351593.124

James F Clark, Philippe Soriano

{"title":"Diverse Fgfr1 signaling pathways and endocytic trafficking regulate mesoderm development.","authors":"James F Clark, Philippe Soriano","doi":"10.1101/gad.351593.124","DOIUrl":"10.1101/gad.351593.124","url":null,"abstract":"The fibroblast growth factor (FGF) pathway is a conserved signaling pathway required for embryonic development. Activated FGF receptor 1 (FGFR1) drives multiple intracellular signaling cascade pathways, including ERK/MAPK and PI3K/AKT, collectively termed canonical signaling. However, unlike Fgfr1-null embryos, embryos containing hypomorphic mutations in Fgfr1 lacking the ability to activate canonical downstream signals are still able to develop to birth but exhibit severe defects in all mesodermal-derived tissues. The introduction of an additional signaling mutation further reduces the activity of Fgfr1, leading to earlier lethality, reduced somitogenesis, and more severe changes in transcriptional outputs. Genes involved in migration, ECM interaction, and phosphoinositol signaling were significantly downregulated, proteomic analysis identified changes in interactions with endocytic pathway components, and cells expressing mutant receptors show changes in endocytic trafficking. Together, we identified processes regulating early mesoderm development by mechanisms involving both canonical and noncanonical Fgfr1 pathways, including direct interaction with cell adhesion components and endocytic regulation.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"393-414"},"PeriodicalIF":7.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247746","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}

引用次数: 0

Glioblastoma microenvironment-from biology to therapy. 胶质母细胞瘤微环境--从生物学到治疗。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-06-25 DOI: 10.1101/gad.351427.123

Renee D Read, Zoe M Tapp, Prajwal Rajappa, Dolores Hambardzumyan

引用次数: 0

Drosophila melanogaster Set8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation. 黑腹果蝇 Set8 和 L(3)mbt 在基因表达中的功能与组蛋白 H4 赖氨酸 20 甲基化无关。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-06-25 DOI: 10.1101/gad.351698.124

Aaron T Crain, Megan B Butler, Christina A Hill, Mai Huynh, Robert K McGinty, Robert J Duronio

{"title":"Drosophila melanogaster Set8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation.","authors":"Aaron T Crain, Megan B Butler, Christina A Hill, Mai Huynh, Robert K McGinty, Robert J Duronio","doi":"10.1101/gad.351698.124","DOIUrl":"10.1101/gad.351698.124","url":null,"abstract":"Monomethylation of lysine 20 of histone H4 (H4K20me1) is catalyzed by Set8 and thought to play important roles in many aspects of genome function that are mediated by H4K20me binding proteins. We interrogated this model in a developing animal by comparing in parallel the transcriptomes of Set8 null , H4 K20R/A , and l(3)mbt mutant Drosophila melanogaster We found that the gene expression profiles of H4 K20A and H4 K20R larvae are markedly different than Set8 null larvae despite similar reductions in H4K20me1. Set8 null mutant cells have a severely disrupted transcriptome and fail to proliferate in vivo, but these phenotypes are not recapitulated by mutation of H4 K20 , indicating that the developmental defects of Set8 null animals are largely due to H4K20me1-independent effects on gene expression. Furthermore, the H4K20me1 binding protein L(3)mbt is recruited to the transcription start sites of most genes independently of H4K20me even though genes bound by L(3)mbt have high levels of H4K20me1. Moreover, both Set8 and L(3)mbt bind to purified H4K20R nucleosomes in vitro. We conclude that gene expression changes in Set8 null and H4 K20 mutants cannot be explained by loss of H4K20me1 or L(3)mbt binding to chromatin and therefore that H4K20me1 does not play a large role in gene expression.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"455-472"},"PeriodicalIF":7.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310505","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}

引用次数: 0

Genome organization regulates nuclear pore complex formation and promotes differentiation during Drosophila oogenesis. 基因组组织调节核孔复合体的形成，并促进果蝇卵子发生过程中的分化。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-06-25 DOI: 10.1101/gad.351402.123

Noor M Kotb, Gulay Ulukaya, Ankita Chavan, Son C Nguyen, Lydia Proskauer, Eric F Joyce, Dan Hasson, Madhav Jagannathan, Prashanth Rangan

{"title":"Genome organization regulates nuclear pore complex formation and promotes differentiation during Drosophila oogenesis.","authors":"Noor M Kotb, Gulay Ulukaya, Ankita Chavan, Son C Nguyen, Lydia Proskauer, Eric F Joyce, Dan Hasson, Madhav Jagannathan, Prashanth Rangan","doi":"10.1101/gad.351402.123","DOIUrl":"10.1101/gad.351402.123","url":null,"abstract":"Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ cell genes during differentiation, and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we found that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ cell genes into a silenced state and activating a group of oocyte genes and nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, cross-talk between genome architecture and NPCs is essential for successful cell fate transitions.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"436-454"},"PeriodicalIF":7.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312734","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}

引用次数: 0

A nuclear architecture screen in Drosophila identifies Stonewall as a link between chromatin position at the nuclear periphery and germline stem cell fate. 果蝇核结构筛选发现，石墙（Stonewall）是核边缘染色质位置与生殖干细胞命运之间的纽带。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-06-25 DOI: 10.1101/gad.351424.123

Ankita Chavan, Randi Isenhart, Son C Nguyen, Noor M Kotb, Jailynn Harke, Anna Sintsova, Gulay Ulukaya, Federico Uliana, Caroline Ashiono, Ulrike Kutay, Gianluca Pegoraro, Prashanth Rangan, Eric F Joyce, Madhav Jagannathan

{"title":"A nuclear architecture screen in Drosophila identifies Stonewall as a link between chromatin position at the nuclear periphery and germline stem cell fate.","authors":"Ankita Chavan, Randi Isenhart, Son C Nguyen, Noor M Kotb, Jailynn Harke, Anna Sintsova, Gulay Ulukaya, Federico Uliana, Caroline Ashiono, Ulrike Kutay, Gianluca Pegoraro, Prashanth Rangan, Eric F Joyce, Madhav Jagannathan","doi":"10.1101/gad.351424.123","DOIUrl":"10.1101/gad.351424.123","url":null,"abstract":"The association of genomic loci to the nuclear periphery is proposed to facilitate cell type-specific gene repression and influence cell fate decisions. However, the interplay between gene position and expression remains incompletely understood, in part because the proteins that position genomic loci at the nuclear periphery remain unidentified. Here, we used an Oligopaint-based HiDRO screen targeting ∼1000 genes to discover novel regulators of nuclear architecture in Drosophila cells. We identified the heterochromatin-associated protein Stonewall (Stwl) as a factor promoting perinuclear chromatin positioning. In female germline stem cells (GSCs), Stwl binds and positions chromatin loci, including GSC differentiation genes, at the nuclear periphery. Strikingly, Stwl-dependent perinuclear positioning is associated with transcriptional repression, highlighting a likely mechanism for Stwl's known role in GSC maintenance and ovary homeostasis. Thus, our study identifies perinuclear anchors in Drosophila and demonstrates the importance of gene repression at the nuclear periphery for cell fate.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"415-435"},"PeriodicalIF":7.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310506","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}

引用次数: 0

Beyond histones: the elusive substrates of chromatin regulators. 组蛋白之外：染色质调节剂难以捉摸的底物。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-06-25 DOI: 10.1101/gad.351969.124

Mattias Mannervik

引用次数: 0

Corrigendum: The evolutionary turnover of recombination hot spots contributes to speciation in mice. 更正：重组热点的进化更替促成了小鼠的物种分化。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-06-01 DOI: 10.1101/gad.352049.124

Fatima Smagulova, Kevin Brick, Yongmei Pu, R Daniel Camerini-Otero, Galina V Petukhova

引用次数: 0

H2A.Z chaperones converge on E2F target genes for melanoma cell proliferation. H2A.Z伴侣会聚到黑色素瘤细胞增殖的E2F靶基因上。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-05-21 DOI: 10.1101/gad.351318.123

Sina Jostes, Chiara Vardabasso, Joanna Dong, Saul Carcamo, Rajendra Singh, Robert Phelps, Austin Meadows, Elena Grossi, Dan Hasson, Emily Bernstein

{"title":"H2A.Z chaperones converge on E2F target genes for melanoma cell proliferation.","authors":"Sina Jostes, Chiara Vardabasso, Joanna Dong, Saul Carcamo, Rajendra Singh, Robert Phelps, Austin Meadows, Elena Grossi, Dan Hasson, Emily Bernstein","doi":"10.1101/gad.351318.123","DOIUrl":"10.1101/gad.351318.123","url":null,"abstract":"High levels of H2A.Z promote melanoma cell proliferation and correlate with poor prognosis. However, the role of the two distinct H2A.Z histone chaperone complexes SRCAP and P400-TIP60 in melanoma remains unclear. Here, we show that individual subunit depletion of SRCAP, P400, and VPS72 (YL1) results in not only the loss of H2A.Z deposition into chromatin but also a reduction of H4 acetylation in melanoma cells. This loss of H4 acetylation is particularly found at the promoters of cell cycle genes directly bound by H2A.Z and its chaperones, suggesting a coordinated regulation between H2A.Z deposition and H4 acetylation to promote their expression. Knockdown of each of the three subunits downregulates E2F1 and its targets, resulting in a cell cycle arrest akin to H2A.Z depletion. However, unlike H2A.Z deficiency, loss of the shared H2A.Z chaperone subunit YL1 induces apoptosis. Furthermore, YL1 is overexpressed in melanoma tissues, and its upregulation is associated with poor patient outcome. Together, these findings provide a rationale for future targeting of H2A.Z chaperones as an epigenetic strategy for melanoma treatment.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"336-353"},"PeriodicalIF":7.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921600","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}

引用次数: 0

Intron lariat spliceosomes convert lariats to true circles: implications for intron transposition. 内含子裂片剪接体将裂片转化为真圆：对内含子转位的影响。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-05-21 DOI: 10.1101/gad.351764.124

Manuel Ares, Haller Igel, Sol Katzman, John P Donohue

引用次数: 0