Genes & development最新文献_第8页

Psat1-generated α-ketoglutarate and glutamine promote muscle stem cell activation and regeneration. Psat1产生的α-酮戊二酸和谷氨酰胺能促进肌肉干细胞的活化和再生。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-03-22 DOI: 10.1101/gad.351428.123

Veronica Ciuffoli, Xuesong Feng, Kan Jiang, Natalia Acevedo-Luna, Kyung Dae Ko, A Hong Jun Wang, Giulia Riparini, Mamduh Khateb, Brian Glancy, Stefania Dell'Orso, Vittorio Sartorelli

{"title":"Psat1-generated α-ketoglutarate and glutamine promote muscle stem cell activation and regeneration.","authors":"Veronica Ciuffoli, Xuesong Feng, Kan Jiang, Natalia Acevedo-Luna, Kyung Dae Ko, A Hong Jun Wang, Giulia Riparini, Mamduh Khateb, Brian Glancy, Stefania Dell'Orso, Vittorio Sartorelli","doi":"10.1101/gad.351428.123","DOIUrl":"10.1101/gad.351428.123","url":null,"abstract":"By satisfying bioenergetic demands, generating biomass, and providing metabolites serving as cofactors for chromatin modifiers, metabolism regulates adult stem cell biology. Here, we report that a branch of glycolysis, the serine biosynthesis pathway (SBP), is activated in regenerating muscle stem cells (MuSCs). Gene inactivation and metabolomics revealed that Psat1, one of the three SBP enzymes, controls MuSC activation and expansion of myogenic progenitors through production of the metabolite α-ketoglutarate (α-KG) and α-KG-generated glutamine. Psat1 ablation resulted in defective expansion of MuSCs and impaired regeneration. Psat1, α-KG, and glutamine were reduced in MuSCs of old mice. α-KG or glutamine re-established appropriate muscle regeneration of adult conditional Psat1 -/- mice and of old mice. These findings contribute insights into the metabolic role of Psat1 during muscle regeneration and suggest α-KG and glutamine as potential therapeutic interventions to ameliorate muscle regeneration during aging.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"151-167"},"PeriodicalIF":7.5,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059113","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

ADNP modulates SINE B2-derived CTCF-binding sites during blastocyst formation in mice. 在小鼠胚泡形成过程中，ADNP 可调节 SINE B2 衍生的 CTCF 结合位点。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-03-22 DOI: 10.1101/gad.351189.123

Wen Wang, Rui Gao, Dongxu Yang, Mingli Ma, Ruge Zang, Xiangxiu Wang, Chuan Chen, Xiaochen Kou, Yanhong Zhao, Jiayu Chen, Xuelian Liu, Jiaxu Lu, Ben Xu, Juntao Liu, Yanxin Huang, Chaoqun Chen, Hong Wang, Shaorong Gao, Yong Zhang, Yawei Gao

{"title":"ADNP modulates SINE B2-derived CTCF-binding sites during blastocyst formation in mice.","authors":"Wen Wang, Rui Gao, Dongxu Yang, Mingli Ma, Ruge Zang, Xiangxiu Wang, Chuan Chen, Xiaochen Kou, Yanhong Zhao, Jiayu Chen, Xuelian Liu, Jiaxu Lu, Ben Xu, Juntao Liu, Yanxin Huang, Chaoqun Chen, Hong Wang, Shaorong Gao, Yong Zhang, Yawei Gao","doi":"10.1101/gad.351189.123","DOIUrl":"10.1101/gad.351189.123","url":null,"abstract":"CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF-anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short interspersed element (SINE) family B2 that are restricted to the cleavage stages. Notably, we discovered that the neuroprotective protein ADNP counteracts the stable association of CTCF at SINE B2-derived CTCF-binding sites. Knockout of Adnp in the zygote led to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 during the morula-to-blastocyst transition, which further led to unfaithful cell differentiation in embryos around implantation. Our analysis highlights an ADNP-dependent restriction of CTCF binding during cell differentiation in preimplantation embryos. Furthermore, our findings shed light on the functional importance of transposable elements (TEs) in promoting genetic innovation and actively shaping the early embryo developmental process specific to mammals.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"168-188"},"PeriodicalIF":7.5,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119233","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

Coordination of histone chaperones for parental histone segregation and epigenetic inheritance. 组蛋白伴侣在亲代组蛋白分离和表观遗传中的协调作用

IF 7.5 1区生物学

Genes & development Pub Date : 2024-03-22 DOI: 10.1101/gad.351278.123

Yimeng Fang, Xu Hua, Chun-Min Shan, Takenori Toda, Feng Qiao, Zhiguo Zhang, Songtao Jia

{"title":"Coordination of histone chaperones for parental histone segregation and epigenetic inheritance.","authors":"Yimeng Fang, Xu Hua, Chun-Min Shan, Takenori Toda, Feng Qiao, Zhiguo Zhang, Songtao Jia","doi":"10.1101/gad.351278.123","DOIUrl":"10.1101/gad.351278.123","url":null,"abstract":"Chromatin-based epigenetic memory relies on the accurate distribution of parental histone H3-H4 tetramers to newly replicated DNA strands. Mcm2, a subunit of the replicative helicase, and Dpb3/4, subunits of DNA polymerase ε, govern parental histone H3-H4 deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here, using fission yeast heterochromatin inheritance systems that eliminate interference from initiation pathways, we show that a Mcm2 histone binding mutation severely disrupts heterochromatin inheritance, while mutations in Dpb3/4 cause only moderate defects. Surprisingly, simultaneous mutations of Mcm2 and Dpb3/4 stabilize heterochromatin inheritance. eSPAN (enrichment and sequencing of protein-associated nascent DNA) analyses confirmed the conservation of Mcm2 and Dpb3/4 functions in parental histone H3-H4 segregation, with their combined absence showing a more symmetric distribution of parental histone H3-H4 than either single mutation alone. Furthermore, the FACT histone chaperone regulates parental histone transfer to both strands and collaborates with Mcm2 and Dpb3/4 to maintain parental histone H3-H4 density and faithful heterochromatin inheritance. These results underscore the importance of both symmetric distribution of parental histones and their density at daughter strands for epigenetic inheritance and unveil distinctive properties of parental histone chaperones during DNA replication.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"189-204"},"PeriodicalIF":7.5,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119234","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

NFATC2IP is a mediator of SUMO-dependent genome integrity NFATC2IP 是依赖于 SUMO 的基因组完整性的介质

IF 10.5 1区生物学

Genes & development Pub Date : 2024-03-19 DOI: 10.1101/gad.350914.123

Tiffany Cho, Lisa Hoeg, Dheva Setiaputra, Daniel Durocher

{"title":"NFATC2IP is a mediator of SUMO-dependent genome integrity","authors":"Tiffany Cho, Lisa Hoeg, Dheva Setiaputra, Daniel Durocher","doi":"10.1101/gad.350914.123","DOIUrl":"https://doi.org/10.1101/gad.350914.123","url":null,"abstract":"The post-translational modification of proteins by SUMO is crucial for cellular viability and mammalian development in part due to the contribution of SUMOylation to genome duplication and repair. To investigate the mechanisms underpinning the essential function of SUMO, we undertook a genome-scale CRISPR/Cas9 screen probing the response to SUMOylation inhibition. This effort identified 130 genes whose disruption reduces or enhances the toxicity of TAK-981, a clinical-stage inhibitor of the SUMO E1-activating enzyme. Among the strongest hits, we validated and characterized NFATC2IP, an evolutionarily conserved protein related to the fungal Esc2 and Rad60 proteins that harbors tandem SUMO-like domains. Cells lacking NFATC2IP are viable but are hypersensitive to SUMO E1 inhibition, likely due to the accumulation of mitotic chromosome bridges and micronuclei. NFATC2IP primarily acts in interphase and associates with nascent DNA, suggesting a role in the postreplicative resolution of replication or recombination intermediates. Mechanistically, NFATC2IP interacts with the SMC5/6 complex and UBC9, the SUMO E2, via its first and second SUMO-like domains, respectively. AlphaFold-Multimer modeling suggests that NFATC2IP positions and activates the UBC9–NSMCE2 complex, the SUMO E3 ligase associated with SMC5/SMC6. We conclude that NFATC2IP is a key mediator of SUMO-dependent genomic integrity that collaborates with the SMC5/6 complex.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"41 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140164691","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

Protein domains of low sequence complexity—dark matter of the proteome 序列复杂度低的蛋白质结构域--蛋白质组中的暗物质

IF 10.5 1区生物学

Genes & development Pub Date : 2024-03-19 DOI: 10.1101/gad.351465.123

Steven L. McKnight

引用次数: 0

WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases WRN 外切酶使 Y 家族 DNA 聚合酶的转座子合成具有高保真性

IF 10.5 1区生物学

Genes & development Pub Date : 2024-03-19 DOI: 10.1101/gad.351410.123

Jung-Hoon Yoon, Karthi Sellamuthu, Louise Prakash, Satya Prakash

{"title":"WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases","authors":"Jung-Hoon Yoon, Karthi Sellamuthu, Louise Prakash, Satya Prakash","doi":"10.1101/gad.351410.123","DOIUrl":"https://doi.org/10.1101/gad.351410.123","url":null,"abstract":"Purified translesion synthesis (TLS) DNA polymerases (Pols) replicate through DNA lesions with a low fidelity; however, TLS operates in a predominantly error-free manner in normal human cells. To explain this incongruity, here we determine whether Y family Pols, which play an eminent role in replication through a diversity of DNA lesions, are incorporated into a multiprotein ensemble and whether the intrinsically high error rate of the TLS Pol is ameliorated by the components in the ensemble. To this end, we provide evidence for an indispensable role of Werner syndrome protein (WRN) and WRN-interacting protein 1 (WRNIP1) in Rev1-dependent TLS by Y family Polη, Polι, or Polκ and show that WRN, WRNIP1, and Rev1 assemble together with Y family Pols in response to DNA damage. Importantly, we identify a crucial role of WRN's 3′ → 5′ exonuclease activity in imparting high fidelity on TLS by Y family Pols in human cells, as the Y family Pols that accomplish TLS in an error-free manner manifest high mutagenicity in the absence of WRN's exonuclease function. Thus, by enforcing high fidelity on TLS Pols, TLS mechanisms have been adapted to safeguard against genome instability and tumorigenesis.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"85 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140164719","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

Corrigendium: Effects of RAS on the genesis of embryonal rhabdomyosarcoma Corrigendium：RAS对胚胎横纹肌肉瘤发病的影响

IF 10.5 1区生物学

Genes & development Pub Date : 2024-03-01 DOI: 10.1101/gad.351747.124

David M. Langenau, Matthew D. Keefe, Narie Y. Storer, Jeffrey R. Guyon, Jeffery L. Kutok, Xiuning Le, Wolfram Goessling, Donna S. Neuberg, Louis M. Kunkel, Leonard I. Zon

引用次数: 0

ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline ATF7IP2/MCAF2 在雄性生殖系中指导 H3K9 甲基化和减数分裂基因调控

IF 10.5 1区生物学

Genes & development Pub Date : 2024-02-21 DOI: 10.1101/gad.351569.124

Kris G. Alavattam, Jasmine M. Esparza, Mengwen Hu, Ryuki Shimada, Anna R. Kohrs, Hironori Abe, Yasuhisa Munakata, Kai Otsuka, Saori Yoshimura, Yuka Kitamura, Yu-Han Yeh, Yueh-Chiang Hu, Jihye Kim, Paul R. Andreassen, Kei-ichiro Ishiguro, Satoshi H. Namekawa

{"title":"ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline","authors":"Kris G. Alavattam, Jasmine M. Esparza, Mengwen Hu, Ryuki Shimada, Anna R. Kohrs, Hironori Abe, Yasuhisa Munakata, Kai Otsuka, Saori Yoshimura, Yuka Kitamura, Yu-Han Yeh, Yueh-Chiang Hu, Jihye Kim, Paul R. Andreassen, Kei-ichiro Ishiguro, Satoshi H. Namekawa","doi":"10.1101/gad.351569.124","DOIUrl":"https://doi.org/10.1101/gad.351569.124","url":null,"abstract":"H3K9 trimethylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that in male meiosis, ATF7IP2 amasses on autosomal and X-pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X-pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein's essential roles in the maintenance of MSCI, suppression of retrotransposons, and global up-regulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"33 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139915809","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 damage remodels the MITF interactome to increase melanoma genomic instability. DNA 损伤重塑了 MITF 相互作用组，从而增加了黑色素瘤基因组的不稳定性。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-02-13 DOI: 10.1101/gad.350740.123

Romuald Binet, Jean-Philippe Lambert, Marketa Tomkova, Samuel Tischfield, Arianna Baggiolini, Sarah Picaud, Sovan Sarkar, Pakavarin Louphrasitthiphol, Diogo Dias, Suzanne Carreira, Timothy C Humphrey, Panagis Fillipakopoulos, Richard White, Colin R Goding

{"title":"DNA damage remodels the MITF interactome to increase melanoma genomic instability.","authors":"Romuald Binet, Jean-Philippe Lambert, Marketa Tomkova, Samuel Tischfield, Arianna Baggiolini, Sarah Picaud, Sovan Sarkar, Pakavarin Louphrasitthiphol, Diogo Dias, Suzanne Carreira, Timothy C Humphrey, Panagis Fillipakopoulos, Richard White, Colin R Goding","doi":"10.1101/gad.350740.123","DOIUrl":"10.1101/gad.350740.123","url":null,"abstract":"Since genome instability can drive cancer initiation and progression, cells have evolved highly effective and ubiquitous DNA damage response (DDR) programs. However, some cells (for example, in skin) are normally exposed to high levels of DNA-damaging agents. Whether such high-risk cells possess lineage-specific mechanisms that tailor DNA repair to the tissue remains largely unknown. Using melanoma as a model, we show here that the microphthalmia-associated transcription factor MITF, a lineage addition oncogene that coordinates many aspects of melanocyte and melanoma biology, plays a nontranscriptional role in shaping the DDR. On exposure to DNA-damaging agents, MITF is phosphorylated at S325, and its interactome is dramatically remodeled; most transcription cofactors dissociate, and instead MITF interacts with the MRE11-RAD50-NBS1 (MRN) complex. Consequently, cells with high MITF levels accumulate stalled replication forks and display defects in homologous recombination-mediated repair associated with impaired MRN recruitment to DNA damage. In agreement with this, high MITF levels are associated with increased single-nucleotide and copy number variant burdens in melanoma. Significantly, the SUMOylation-defective MITF-E318K melanoma predisposition mutation recapitulates the effects of DNA-PKcs-phosphorylated MITF. Our data suggest that a nontranscriptional function of a lineage-restricted transcription factor contributes to a tissue-specialized modulation of the DDR that can impact cancer initiation.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"70-94"},"PeriodicalIF":7.5,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691635","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

Spore germination: Two ion channels are better than one. 孢子发芽两个离子通道胜过一个

IF 7.5 1区生物学

Genes & development Pub Date : 2024-02-13 DOI: 10.1101/gad.351554.124

Patrick Eichenberger

引用次数: 0