PLoS Genetics最新文献_第7页

Correction: The bZIP transcription factor AREB3 mediates FT signalling and floral transition at the Arabidopsis shoot apical meristem. 更正:bZIP转录因子AREB3介导拟南芥茎尖分生组织的FT信号传导和花的转变。

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-08-01 DOI: 10.1371/journal.pgen.1010920

Damiano Martignago, Vítor da Silveira Falavigna, Alessandra Lombardi, He Gao, Paolo Korwin Krukowski, Massimo Galbiati, Chiara Tonelli, George Coupland, Lucio Conti

引用次数: 0

Emergence of linkage between cooperative RNA replicators encoding replication and metabolic enzymes through experimental evolution. 通过实验进化，编码复制和代谢酶的合作RNA复制子之间出现了连锁。

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-08-01 DOI: 10.1371/journal.pgen.1010471

Kensuke Ueda, Ryo Mizuuchi, Norikazu Ichihashi

{"title":"Emergence of linkage between cooperative RNA replicators encoding replication and metabolic enzymes through experimental evolution.","authors":"Kensuke Ueda, Ryo Mizuuchi, Norikazu Ichihashi","doi":"10.1371/journal.pgen.1010471","DOIUrl":"https://doi.org/10.1371/journal.pgen.1010471","url":null,"abstract":"The integration of individually replicating genes into a primitive chromosome is a key evolutionary transition in the development of life, allowing the simultaneous inheritance of genes. However, how this transition occurred is unclear because the extended size of primitive chromosomes replicate slower than unlinked genes. Theoretical studies have suggested that a primitive chromosome can evolve in the presence of cell-like compartments, as the physical linkage prevents the stochastic loss of essential genes upon division, but experimental support for this is lacking. Here, we demonstrate the evolution of a chromosome-like RNA from two cooperative RNA replicators encoding replication and metabolic enzymes. Through their long-term replication in cell-like compartments, linked RNAs emerged with the two cooperative RNAs connected end-to-end. The linked RNAs had different mutation patterns than the two unlinked RNAs, suggesting that they were maintained as partially distinct lineages in the population. Our results provide experimental evidence supporting the plausibility of the evolution of a primitive chromosome from unlinked gene fragments, an important step in the emergence of complex biological systems.","PeriodicalId":20266,"journal":{"name":"PLoS Genetics","volume":"19 8","pages":"e1010471"},"PeriodicalIF":4.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10032995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 1

The DNMT3A ADD domain is required for efficient de novo DNA methylation and maternal imprinting in mouse oocytes. DNMT3A ADD结构域是小鼠卵母细胞中有效的DNA从头甲基化和母体印迹所必需的。

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-08-01 DOI: 10.1371/journal.pgen.1010855

Ryuji Uehara, Wan Kin Au Yeung, Keisuke Toriyama, Hiroaki Ohishi, Naoki Kubo, Hidehiro Toh, Isao Suetake, Kenjiro Shirane, Hiroyuki Sasaki

{"title":"The DNMT3A ADD domain is required for efficient de novo DNA methylation and maternal imprinting in mouse oocytes.","authors":"Ryuji Uehara, Wan Kin Au Yeung, Keisuke Toriyama, Hiroaki Ohishi, Naoki Kubo, Hidehiro Toh, Isao Suetake, Kenjiro Shirane, Hiroyuki Sasaki","doi":"10.1371/journal.pgen.1010855","DOIUrl":"https://doi.org/10.1371/journal.pgen.1010855","url":null,"abstract":"Establishment of a proper DNA methylation landscape in mammalian oocytes is important for maternal imprinting and embryonic development. De novo DNA methylation in oocytes is mediated by the DNA methyltransferase DNMT3A, which has an ATRX-DNMT3-DNMT3L (ADD) domain that interacts with histone H3 tail unmethylated at lysine-4 (H3K4me0). The domain normally blocks the methyltransferase domain via intramolecular interaction and binding to histone H3K4me0 releases the autoinhibition. However, H3K4me0 is widespread in chromatin and the role of the ADD-histone interaction has not been studied in vivo. We herein show that amino-acid substitutions in the ADD domain of mouse DNMT3A cause dwarfism. Oocytes derived from homozygous females show mosaic loss of CG methylation and almost complete loss of non-CG methylation. Embryos derived from such oocytes die in mid-to-late gestation, with stochastic and often all-or-none-type CG-methylation loss at imprinting control regions and misexpression of the linked genes. The stochastic loss is a two-step process, with loss occurring in cleavage-stage embryos and regaining occurring after implantation. These results highlight an important role for the ADD domain in efficient, and likely processive, de novo CG methylation and pose a model for stochastic inheritance of epigenetic perturbations in germ cells to the next generation.","PeriodicalId":20266,"journal":{"name":"PLoS Genetics","volume":"19 8","pages":"e1010855"},"PeriodicalIF":4.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9932695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 2

A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases. 一个识别细胞类型的统计框架，其基因调节比例与复杂疾病相关。

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-07-31 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pgen.1010825

Wei Liu, Wenxuan Deng, Ming Chen, Zihan Dong, Biqing Zhu, Zhaolong Yu, Daiwei Tang, Maor Sauler, Chen Lin, Louise V Wain, Michael H Cho, Naftali Kaminski, Hongyu Zhao

{"title":"A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases.","authors":"Wei Liu, Wenxuan Deng, Ming Chen, Zihan Dong, Biqing Zhu, Zhaolong Yu, Daiwei Tang, Maor Sauler, Chen Lin, Louise V Wain, Michael H Cho, Naftali Kaminski, Hongyu Zhao","doi":"10.1371/journal.pgen.1010825","DOIUrl":"10.1371/journal.pgen.1010825","url":null,"abstract":"Finding disease-relevant tissues and cell types can facilitate the identification and investigation of functional genes and variants. In particular, cell type proportions can serve as potential disease predictive biomarkers. In this manuscript, we introduce a novel statistical framework, cell-type Wide Association Study (cWAS), that integrates genetic data with transcriptomics data to identify cell types whose genetically regulated proportions (GRPs) are disease/trait-associated. On simulated and real GWAS data, cWAS showed good statistical power with newly identified significant GRP associations in disease-associated tissues. More specifically, GRPs of endothelial and myofibroblasts in lung tissue were associated with Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease, respectively. For breast cancer, the GRP of blood CD8+ T cells was negatively associated with breast cancer (BC) risk as well as survival. Overall, cWAS is a powerful tool to reveal cell types associated with complex diseases mediated by GRPs.","PeriodicalId":20266,"journal":{"name":"PLoS Genetics","volume":"19 7","pages":"e1010825"},"PeriodicalIF":4.5,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin. Diversity Outbred小鼠的脂质体QTL确定了α/β水解酶结构域2（Abhd2）作为代谢磷脂酰胆碱和心磷脂的酶的新功能。

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-07-31 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pgen.1010713

Tara R Price, Donnie S Stapleton, Kathryn L Schueler, Marie K Norris, Brian W Parks, Brian S Yandell, Gary A Churchill, William L Holland, Mark P Keller, Alan D Attie

{"title":"Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin.","authors":"Tara R Price, Donnie S Stapleton, Kathryn L Schueler, Marie K Norris, Brian W Parks, Brian S Yandell, Gary A Churchill, William L Holland, Mark P Keller, Alan D Attie","doi":"10.1371/journal.pgen.1010713","DOIUrl":"10.1371/journal.pgen.1010713","url":null,"abstract":"We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/β-hydrolase domain 2 (Abhd2), one of 23 members of the ABHD gene family. We validated this observation by measuring lipids in a mouse with a whole-body deletion of Abhd2. The Abhd2KO mice had a significant increase in liver levels of phosphatidylcholine and phosphatidylethanolamine. Unexpectedly, we also found a decrease in two key mitochondrial lipids, cardiolipin and phosphatidylglycerol, in male Abhd2KO mice. These data suggest that Abhd2 plays a role in the synthesis, turnover, or remodeling of liver phospholipids.","PeriodicalId":20266,"journal":{"name":"PLoS Genetics","volume":"19 7","pages":"e1010713"},"PeriodicalIF":4.5,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

DHX38 restricts chemoresistance by regulating the alternative pre-mRNA splicing of RELL2 in pancreatic ductal adenocarcinoma. DHX38通过调节胰腺导管腺癌中RELL2的前mRNA替代剪接限制化疗抗性

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-07-28 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pgen.1010847

Zeru Li, Cheng Qin, Bangbo Zhao, Yuanyang Wang, Tianyu Li, Yutong Zhao, Weibin Wang

{"title":"DHX38 restricts chemoresistance by regulating the alternative pre-mRNA splicing of RELL2 in pancreatic ductal adenocarcinoma.","authors":"Zeru Li, Cheng Qin, Bangbo Zhao, Yuanyang Wang, Tianyu Li, Yutong Zhao, Weibin Wang","doi":"10.1371/journal.pgen.1010847","DOIUrl":"10.1371/journal.pgen.1010847","url":null,"abstract":"Intron retention plays an important role in cancer progression and chemotherapy resistance and seems to be essential for the maintenance of genome stability in cancer. Here, our goal was to analyze the role of receptor expressed in lymphoid tissue (Relt)-like 2 (RELL2) intron 4 retention in promoting pancreatic ductal adenocarcinoma (PDAC) progression. Our results showed that intron retention (IR) occurs at the fourth intron of RELL2 transcript in gemcitabine resistant PDAC cells, however, the regulatory mechanism and the clinical implications of IR of RELL2 are unclear. Firstly, we found that RELL2 plays an anti-oncogenic role in PDAC by performing in vitro functional assays including cell proliferation, GEM cytotoxicity assay and apoptosis. Subsequently, we identified the upstream gene of RELL2, DEAH-Box Helicase 38 (DHX38), and demonstrated the direct interaction between DHX38 and RELL2 by RIP-qPCR. We also found that altered expression of DHX38 resulted in corresponding changes in intron 4 retention of RELL2. Importantly, we unveiled that overexpression of DHX38 on the basis of knocking down of the fourth intron of RELL2 resulted in an impaired intron 4 intention. Overall, our study identified a new IR site in PDAC, which could be a possible target for PDAC therapy.","PeriodicalId":20266,"journal":{"name":"PLoS Genetics","volume":"19 7","pages":"e1010847"},"PeriodicalIF":4.5,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9958184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 2

Identification of the nuclear localization signal in the Saccharomyces cerevisiae Pif1 DNA helicase. 鉴定酿酒酵母 Pif1 DNA 螺旋酶的核定位信号。

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-07-24 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pgen.1010853

Rosemary S Lee, Carly L Geronimo, Liping Liu, Jerzy M Twarowski, Anna Malkova, Virginia A Zakian

{"title":"Identification of the nuclear localization signal in the Saccharomyces cerevisiae Pif1 DNA helicase.","authors":"Rosemary S Lee, Carly L Geronimo, Liping Liu, Jerzy M Twarowski, Anna Malkova, Virginia A Zakian","doi":"10.1371/journal.pgen.1010853","DOIUrl":"10.1371/journal.pgen.1010853","url":null,"abstract":"Saccharomyces cerevisiae Pif1 is a multi-functional DNA helicase that plays diverse roles in the maintenance of the nuclear and mitochondrial genomes. Two isoforms of Pif1 are generated from a single open reading frame by the use of alternative translational start sites. The Mitochondrial Targeting Signal (MTS) of Pif1 is located between the two start sites, but a Nuclear Localization Signal (NLS) has not been identified. Here we used sequence and functional analysis to identify an NLS element. A mutant allele of PIF1 (pif1-NLSΔ) that lacks four basic amino acids (781KKRK784) in the carboxyl-terminal domain of the 859 amino acid Pif1 was expressed at wild type levels and retained wild type mitochondrial function. However, pif1-NLSΔ cells were defective in four tests for nuclear function: telomere length maintenance, Okazaki fragment processing, break-induced replication (BIR), and binding to nuclear target sites. Fusing the NLS from the simian virus 40 (SV40) T-antigen to the Pif1-NLSΔ protein reduced the nuclear defects of pif1-NLSΔ cells. Thus, four basic amino acids near the carboxyl end of Pif1 are required for the vast majority of nuclear Pif1 function. Our study also reveals phenotypic differences between the previously described loss of function pif1-m2 allele and three other pif1 mutant alleles generated in this work, which will be useful to study nuclear Pif1 functions.","PeriodicalId":20266,"journal":{"name":"PLoS Genetics","volume":"19 7","pages":"e1010853"},"PeriodicalIF":4.5,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Characterization of factors that underlie transcriptional silencing in C. elegans oocytes. 秀丽隐杆线虫卵母细胞转录沉默因素的表征。

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-07-21 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pgen.1010831

Mezmur D Belew, Emilie Chien, W Matthew Michael

{"title":"Characterization of factors that underlie transcriptional silencing in C. elegans oocytes.","authors":"Mezmur D Belew, Emilie Chien, W Matthew Michael","doi":"10.1371/journal.pgen.1010831","DOIUrl":"10.1371/journal.pgen.1010831","url":null,"abstract":"While it has been appreciated for decades that prophase-arrested oocytes are transcriptionally silenced on a global level, the molecular pathways that promote silencing have remained elusive. Previous work in C. elegans has shown that both topoisomerase II (TOP-2) and condensin II collaborate with the H3K9me heterochromatin pathway to silence gene expression in the germline during L1 starvation, and that the PIE-1 protein silences the genome in the P-lineage of early embryos. Here, we show that all three of these silencing systems, TOP-2/condensin II, H3K9me, and PIE-1, are required for transcriptional repression in oocytes. We find that H3K9me3 marks increase dramatically on chromatin during silencing, and that silencing is under cell cycle control. We also find that PIE-1 localizes to the nucleolus just prior to silencing, and that nucleolar dissolution during silencing is dependent on TOP-2/condensin II. Our data identify both the molecular components and the trigger for genome silencing in oocytes and establish a link between PIE-1 nucleolar residency and its ability to repress transcription.","PeriodicalId":20266,"journal":{"name":"PLoS Genetics","volume":"19 7","pages":"e1010831"},"PeriodicalIF":4.5,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9928692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Building the synaptonemal complex: Molecular interactions between the axis and the central region. 构建突触复合体：轴和中心区域之间的分子相互作用。

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-07-20 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pgen.1010822

Spencer G Gordon, Ofer Rog

引用次数: 3

A Van Gogh/Vangl tyrosine phosphorylation switch regulates its interaction with core Planar Cell Polarity factors Prickle and Dishevelled. Van Gogh/Vangl 酪氨酸磷酸化开关调节其与核心平面细胞极性因子 Prickle 和 Dishevelled 的相互作用。

IF 4.5 2区生物学

PLoS Genetics Pub Date : 2023-07-18 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pgen.1010849

Ashley C Humphries, Claudia Molina-Pelayo, Parijat Sil, C Clayton Hazelett, Danelle Devenport, Marek Mlodzik

{"title":"A Van Gogh/Vangl tyrosine phosphorylation switch regulates its interaction with core Planar Cell Polarity factors Prickle and Dishevelled.","authors":"Ashley C Humphries, Claudia Molina-Pelayo, Parijat Sil, C Clayton Hazelett, Danelle Devenport, Marek Mlodzik","doi":"10.1371/journal.pgen.1010849","DOIUrl":"10.1371/journal.pgen.1010849","url":null,"abstract":"Epithelial tissues can be polarized along two axes: in addition to apical-basal polarity they are often also polarized within the plane of the epithelium, known as planar cell polarity (PCP). PCP depends upon the conserved Wnt/Frizzled (Fz) signaling factors, including Fz itself and Van Gogh (Vang/Vangl in mammals). Here, taking advantage of the complementary features of Drosophila wing and mouse skin PCP establishment, we dissect how Vang/Vangl phosphorylation on a specific conserved tyrosine residue affects its interaction with two cytoplasmic core PCP factors, Dishevelled (Dsh/Dvl1-3 in mammals) and Prickle (Pk/Pk1-3). We demonstrate that Pk and Dsh/Dvl bind to Vang/Vangl in an overlapping region centered around this tyrosine. Strikingly, Vang/Vangl phosphorylation promotes its binding to Prickle, a key effector of the Vang/Vangl complex, and inhibits its interaction with Dishevelled. Thus phosphorylation of this tyrosine appears to promote the formation of the mature Vang/Vangl-Pk complex during PCP establishment and conversely it inhibits the Vang interaction with the antagonistic effector Dishevelled. Intriguingly, the phosphorylation state of this tyrosine might thus serve as a switch between transient interactions with Dishevelled and stable formation of Vang-Pk complexes during PCP establishment.","PeriodicalId":20266,"journal":{"name":"PLoS Genetics","volume":"19 7","pages":"e1010849"},"PeriodicalIF":4.5,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10381084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10306589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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