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Transcription of damage-induced RNA in Arabidopsis was frequently initiated from DSB loci within the genic regions 拟南芥中损伤诱导 RNA 的转录经常是从基因区内的 DSB 位点开始的。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-06-07 DOI: 10.1111/gtc.13133
Kohei Kawaguchi, Soichirou Satoh, Junichi Obokata
{"title":"Transcription of damage-induced RNA in Arabidopsis was frequently initiated from DSB loci within the genic regions","authors":"Kohei Kawaguchi,&nbsp;Soichirou Satoh,&nbsp;Junichi Obokata","doi":"10.1111/gtc.13133","DOIUrl":"10.1111/gtc.13133","url":null,"abstract":"<p>DNA double-strand breaks (DSBs) are the most severe DNA lesions and need to be removed immediately to prevent loss of genomic information. Recently, it has been revealed that DSBs induce novel transcription from the cleavage sites in various species, resulting in RNAs being referred to as damage-induced RNAs (diRNAs). While diRNA synthesis is an early event in the DNA damage response and plays an essential role in DSB repair activation, the location where diRNAs are newly generated in plants remains unclear, as does their transcriptional mechanism. Here, we performed the sequencing of polyadenylated (polyA) diRNAs that emerged around all DSB loci in <i>Arabidopsis thaliana</i> under the expression of the exogenous restriction enzyme <i>Sbf</i> I and observed 88 diRNAs transcribed via RNA polymerase II in 360 DSB loci. Most of the detected diRNAs originated within active genes and were transcribed from DSBs in a bidirectional manner. Furthermore, we found that diRNA elongation tends to terminate at the boundary of an endogenous gene located near DSB loci. Our results provide reliable evidence for understanding the importance of new transcription at DSBs and show that diRNA is a crucial factor for successful DSB repair.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 8","pages":"681-689"},"PeriodicalIF":1.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
The HMG-box module in FACT is critical for suppressing epigenetic variegation of heterochromatin in fission yeast FACT中的HMG-box模块对于抑制裂殖酵母异染色质的表观遗传变异至关重要。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-06-05 DOI: 10.1111/gtc.13132
Shinya Takahata, Asahi Taguchi, Ayaka Takenaka, Miyuki Mori, Yuji Chikashige, Chihiro Tsutsumi, Yasushi Hiraoka, Yota Murakami
{"title":"The HMG-box module in FACT is critical for suppressing epigenetic variegation of heterochromatin in fission yeast","authors":"Shinya Takahata,&nbsp;Asahi Taguchi,&nbsp;Ayaka Takenaka,&nbsp;Miyuki Mori,&nbsp;Yuji Chikashige,&nbsp;Chihiro Tsutsumi,&nbsp;Yasushi Hiraoka,&nbsp;Yota Murakami","doi":"10.1111/gtc.13132","DOIUrl":"10.1111/gtc.13132","url":null,"abstract":"<p>Chromatin condensation state is the key for retrieving genetic information. High-mobility group protein (HMG) proteins exhibit DNA-binding and bending activities, playing an important role in the regulation of chromatin structure. We have shown that nucleosomes tightly packaged into heterochromatin undergo considerable dynamic histone H2A-H2B maintenance via the direct interaction between HP1/Swi6 and facilitate chromatin transcription (FACT), which is composed of the Spt16/Pob3 heterodimer and Nhp6. In this study, we analyzed the role of Nhp6, an HMG box protein, in the FACT at heterochromatin. Pob3 mutant strains showed derepressed heterochromatin-dependent gene silencing, whereas Nhp6 mutant strains did not show significant defects in chromatin regulation or gene expression, suggesting that these two modules play different roles in chromatin regulation. We expressed a protein fusing Nhp6 to the C-terminus of Pob3, which mimics the multicellular FACT component Ssrp1. The chromatin-binding activity of FACT increased with the number of Nhp6 fused to Pob3, and the heterochromatin formation rate was promoted more strongly. Furthermore, we demonstrated that this promotion of heterochromatinization inhibited the heterochromatic variegation caused by <i>epe1</i><sup>+</sup> disruption. Heterochromatic variegation can be observed in a variety of regulatory steps; however, when it is caused by fluctuations in chromatin arrangement, it can be eliminated through the strong recruitment of the FACT complex.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 7","pages":"567-583"},"PeriodicalIF":1.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
DNMT1 can induce primary germ layer differentiation through de novo DNA methylation DNMT1 可通过 DNA 的从头甲基化诱导初级生殖层分化。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-05-29 DOI: 10.1111/gtc.13130
Takamasa Ito, Musashi Kubiura-Ichimaru, Fumihito Miura, Shoji Tajima, M. Azim Surani, Takashi Ito, Shinpei Yamaguchi, Masako Tada
{"title":"DNMT1 can induce primary germ layer differentiation through de novo DNA methylation","authors":"Takamasa Ito,&nbsp;Musashi Kubiura-Ichimaru,&nbsp;Fumihito Miura,&nbsp;Shoji Tajima,&nbsp;M. Azim Surani,&nbsp;Takashi Ito,&nbsp;Shinpei Yamaguchi,&nbsp;Masako Tada","doi":"10.1111/gtc.13130","DOIUrl":"10.1111/gtc.13130","url":null,"abstract":"<p>DNA methyltransferases and Ten-Eleven Translocation (TET) proteins regulate the DNA methylation and demethylation cycles during mouse embryonic development. Although DNMT1 mainly plays a role in the maintenance of DNA methylation after DNA replication, it is also reported to possess de novo methyltransferase capacity. However, its physiological significance remains unclear. Here, we demonstrate that full-length DNMT1 (FL) and a mutant lacking the N-terminus necessary for its maintenance activity (602) confer the differentiation potential of mouse <i>Dnmt1</i>, <i>Dnmt3a</i>, and <i>Dnmt3b</i> (Dnmts-TKO) embryonic stem cells (ESCs). Both FL and 602 inhibit the spontaneous differentiation of Dnmts-TKO ESCs in the undifferentiated state. Dnmts-TKO ESCs showed loss of DNA methylation and de-repression of primitive endoderm-related genes, but these defects were partially restored in Dnmts-TKO + FL and Dnmts-TKO + 602 ESCs. Upon differentiation, Dnmts-TKO + FL ESCs show increased 5mC and 5hmC levels across chromosomes, including pericentromeric regions. In contrast, Dnmts-TKO + 602 ESCs didn't accumulate 5mC, and sister chromatids showed 5hmC asynchronously. Furthermore, in comparison with DNMT1_602, DNMT1_FL effectively promoted commitment to the epiblast-like cells and beyond, driving cell-autonomous mesendodermal and germline differentiation through embryoid body-based methods. With precise target selectivity achieved by its N-terminal region, DNMT1 may play a role in gene regulation leading to germline development.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 7","pages":"549-566"},"PeriodicalIF":1.3,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Revisiting the gene mutations and protein profile of WT 9-12: An autosomal dominant polycystic kidney disease cell line 重新审视 WT 9-12 的基因突变和蛋白质特征:常染色体显性多囊肾细胞系
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-05-23 DOI: 10.1111/gtc.13129
Hwa Chia Chai, Rhubaniya Mahendran, Kien Chai Ong, Kek Heng Chua
{"title":"Revisiting the gene mutations and protein profile of WT 9-12: An autosomal dominant polycystic kidney disease cell line","authors":"Hwa Chia Chai,&nbsp;Rhubaniya Mahendran,&nbsp;Kien Chai Ong,&nbsp;Kek Heng Chua","doi":"10.1111/gtc.13129","DOIUrl":"10.1111/gtc.13129","url":null,"abstract":"<p>WT 9-12 is one of the cell lines commonly used for autosomal dominant polycystic kidney disease (ADPKD) studies. Previous studies had described the <i>PKD</i> gene mutations and polycystin expression in WT 9-12. Nonetheless, the mutations occurring in other ADPKD-associated genes have not been investigated. This study aims to revisit these mutations and protein profile of WT 9-12. Whole genome sequencing verified the presence of truncation mutation at amino acid 2556 (Q2556X) in <i>PKD1</i> gene of WT 9-12. Besides, those variations with high impacts included single nucleotide polymorphisms (rs8054182, rs117006360, and rs12925771) and insertions and deletions (InDels) (rs145602984 and rs55980345) in <i>PKD1L2</i>; InDel (rs1296698195) in <i>PKD1L3</i>; and copy number variations in <i>GANAB</i>. Protein profiles generated from the total proteins of WT 9-12 and HK-2 cells were compared using isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Polycystin-1 was absent in WT 9-12. The gene ontology enrichment and reactome pathway analyses revealed that the upregulated and downregulated proteins of WT 9-12 relative to HK-2 cell line leaded to signaling pathways related to immune response and amino acid metabolism, respectively. The ADPKD-related mutations and signaling pathways associated with differentially expressed proteins in WT 9-12 may help researchers in cell line selection for their studies.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 7","pages":"599-607"},"PeriodicalIF":1.3,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Chimera RNA transcribed from integrated HPV18 genome with adjacent host genomic region promotes oncogenic gene expression through condensate formation 从与邻近宿主基因组区域整合的 HPV18 基因组转录的嵌合体 RNA 通过凝集物的形成促进致癌基因的表达。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-05-07 DOI: 10.1111/gtc.13121
Kazuki Furugori, Hidefumi Suzuki, Ryota Abe, Keiko Horiuchi, Tomohiko Akiyama, Tomonori Hirose, Atsushi Toyoda, Hidehisa Takahashi
{"title":"Chimera RNA transcribed from integrated HPV18 genome with adjacent host genomic region promotes oncogenic gene expression through condensate formation","authors":"Kazuki Furugori,&nbsp;Hidefumi Suzuki,&nbsp;Ryota Abe,&nbsp;Keiko Horiuchi,&nbsp;Tomohiko Akiyama,&nbsp;Tomonori Hirose,&nbsp;Atsushi Toyoda,&nbsp;Hidehisa Takahashi","doi":"10.1111/gtc.13121","DOIUrl":"10.1111/gtc.13121","url":null,"abstract":"<p>Most cervical cancers are caused by human papillomavirus (HPV) infection. In HeLa cells, the HPV18 viral genome is integrated at chromosome 8q24.21 and activates transcription of the proto-oncogene <i>c-Myc</i>. However, the mechanism of how the integrated HPV genome and its transcribed RNAs exhibit transcription activation function has not been fully elucidated. In this study, we found that HPV18 transcripts contain an enhancer RNA-like function to activate proximal genes including <i>CCAT1-5L</i> and <i>c-Myc</i>. We showed that the human genome-integrated <i>HPV18</i> genes are activated by transcription coregulators including BRD4 and Mediator. The transcribed HPV18 RNAs form a liquid-like condensate at chromosome 8q24.21 locus, which in turn accumulates RNA polymerase II. Moreover, we focused on a relatively uncharacterized transcript from the <b>u</b>pstream <b>r</b>egion of <i><b>C</b>CAT1</i>, named <i>URC</i>. The <i>URC</i> RNA is transcribed as a chimera RNA with HPV18 and is composed of the 3′-untranslated region of the HPV18 transcript. We experimentally showed that the <i>URC</i> contributes to stabilization of HPV18 RNAs by supplying a polyadenylation site for the HPV18 transcript. Our findings suggest that integrated HPV18 at 8q24.21 locus produces HPV18-URC chimera RNA and promotes tumorigenesis through RNA-based condensate formation.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 7","pages":"532-548"},"PeriodicalIF":1.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Rcn1, the fission yeast homolog of human DSCR1, regulates arsenite tolerance independently from calcineurin Rcn1是人类DSCR1的裂殖酵母同源物,它独立于钙调素调节亚砷酸盐耐受性。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-05-07 DOI: 10.1111/gtc.13122
Teruaki Takasaki, Asuka Bamba, Yuka Kukita, Aiko Nishida, Daiki Kanbayashi, Kanako Hagihara, Ryosuke Satoh, Keiichi Ishihara, Reiko Sugiura
{"title":"Rcn1, the fission yeast homolog of human DSCR1, regulates arsenite tolerance independently from calcineurin","authors":"Teruaki Takasaki,&nbsp;Asuka Bamba,&nbsp;Yuka Kukita,&nbsp;Aiko Nishida,&nbsp;Daiki Kanbayashi,&nbsp;Kanako Hagihara,&nbsp;Ryosuke Satoh,&nbsp;Keiichi Ishihara,&nbsp;Reiko Sugiura","doi":"10.1111/gtc.13122","DOIUrl":"10.1111/gtc.13122","url":null,"abstract":"<p>Calcineurin (CN) is a conserved Ca<sup>2+</sup>/calmodulin-dependent phosphoprotein phosphatase that plays a key role in Ca<sup>2+</sup> signaling. Regulator of calcineurin 1 (RCAN1), also known as Down syndrome critical region gene 1 (DSCR1), interacts with calcineurin and inhibits calcineurin-dependent signaling in various organisms. Ppb1, the fission yeast calcineurin regulates Cl<sup>−</sup>-homeostasis, and Ppb1 deletion induces MgCl<sub>2</sub> hypersensitivity. Here, we characterize the conserved and novel roles of the fission yeast RCAN1 homolog <i>rcn1</i><sup>+</sup>. Consistent with its role as an endogenous calcineurin inhibitor, Rcn1 overproduction reproduced the calcineurin-null phenotypes, including MgCl<sub>2</sub> hypersensitivity and inhibition of calcineurin signaling upon extracellular Ca<sup>2+</sup> stimuli as evaluated by the nuclear translocation and transcriptional activation of the calcineurin substrate Prz1. Notably, overexpression of <i>rcn1</i><sup>+</sup> causes hypersensitivity to arsenite, whereas calcineurin deletion induces arsenite tolerance, showing a phenotypic discrepancy between Rcn1 overexpression and calcineurin deletion. Importantly, although Rcn1 deletion induces modest sensitivities to arsenite and MgCl<sub>2</sub> in wild-type cells, the arsenite tolerance, but not MgCl<sub>2</sub> sensitivity, associated with Ppb1 deletion was markedly suppressed by Rcn1 deletion. Collectively, our findings reveal a previously unrecognized functional collaboration between Rcn1 and calcineurin, wherein Rcn1 not only negatively regulates calcineurin in the Cl<sup>−</sup> homeostasis, but also Rcn1 mediates calcineurin signaling to modulate arsenite cytotoxicity.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 7","pages":"589-598"},"PeriodicalIF":1.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Turnover of EDEM1, an ERAD-enhancing factor, is mediated by multiple degradation routes ERAD增强因子EDEM1的转换由多种降解途径介导
IF 2.1 4区 生物学
Genes to Cells Pub Date : 2024-04-29 DOI: 10.1111/gtc.13117
Riko Katsuki, Mai Kanuka, Ren Ohta, Shusei Yoshida, Taku Tamura
{"title":"Turnover of EDEM1, an ERAD-enhancing factor, is mediated by multiple degradation routes","authors":"Riko Katsuki,&nbsp;Mai Kanuka,&nbsp;Ren Ohta,&nbsp;Shusei Yoshida,&nbsp;Taku Tamura","doi":"10.1111/gtc.13117","DOIUrl":"10.1111/gtc.13117","url":null,"abstract":"<p>Quality-based protein production and degradation in the endoplasmic reticulum (ER) are essential for eukaryotic cell survival. During protein maturation in the ER, misfolded or unassembled proteins are destined for disposal through a process known as ER-associated degradation (ERAD). EDEM1 is an ERAD-accelerating factor whose gene expression is upregulated by the accumulation of aberrant proteins in the ER, known as ER stress. Although the role of EDEM1 in ERAD has been studied in detail, the turnover of EDEM1 by intracellular degradation machinery, including the proteasome and autophagy, is not well understood. To clarify EDEM1 regulation in the protein level, degradation mechanism of EDEM1 was examined. Our results indicate that both ERAD and autophagy degrade EDEM1 alike misfolded degradation substrates, although each degradation machinery targets EDEM1 in different folded states of proteins. We also found that ERAD factors, including the SEL1L/Hrd1 complex, YOD1, XTP3B, ERdj3, VIMP, BAG6, and JB12, but not OS9, are involved in EDEM1 degradation in a mannose-trimming-dependent and -independent manner. Our results suggest that the ERAD accelerating factor, EDEM1, is turned over by the ERAD itself, similar to ERAD clients.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 6","pages":"486-502"},"PeriodicalIF":2.1,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Integrated conjugal plasmid pLS20 in the Bacillus subtilis genome produced 850-kbp circular subgenomes transmissible to another B. subtilis 在枯草芽孢杆菌基因组中整合共轭质粒 pLS20,产生 850 kbp 的环状亚基因组,可传播给另一个枯草芽孢杆菌
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-04-25 DOI: 10.1111/gtc.13120
Mitsuhiro Itaya, Masakazu Kataoka
{"title":"Integrated conjugal plasmid pLS20 in the Bacillus subtilis genome produced 850-kbp circular subgenomes transmissible to another B. subtilis","authors":"Mitsuhiro Itaya,&nbsp;Masakazu Kataoka","doi":"10.1111/gtc.13120","DOIUrl":"10.1111/gtc.13120","url":null,"abstract":"<p><i>Bacillus subtilis</i> was engineered to produce circular subgenomes that are directly transmittable to another <i>B. subtilis</i>. The conjugational plasmid pLS20 integrated into the <i>B. subtilis</i> genome supported not only subgenome replication but also transmission to another <i>B. subtilis</i> species. The subgenome system developed in this study completes a streamlined platform from the synthesis to the transmission of giant DNA by <i>B. subtilis</i>.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 7","pages":"584-588"},"PeriodicalIF":1.3,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140801478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 zinc-finger protein Moc3 functions as a transcription activator to promote RNAi-dependent constitutive heterochromatin establishment in fission yeast 锌指蛋白 Moc3 发挥转录激活剂的功能,促进裂殖酵母中 RNAi- 依赖性组成型异染色质的建立
IF 2.1 4区 生物学
Genes to Cells Pub Date : 2024-04-17 DOI: 10.1111/gtc.13116
Miyuki Mori, Michiaki Sato, Shinya Takahata, Takuya Kajitani, Yota Murakami
{"title":"A zinc-finger protein Moc3 functions as a transcription activator to promote RNAi-dependent constitutive heterochromatin establishment in fission yeast","authors":"Miyuki Mori,&nbsp;Michiaki Sato,&nbsp;Shinya Takahata,&nbsp;Takuya Kajitani,&nbsp;Yota Murakami","doi":"10.1111/gtc.13116","DOIUrl":"10.1111/gtc.13116","url":null,"abstract":"<p>In fission yeast, <i>Schizosaccharomyces pombe,</i> constitutive heterochromatin defined by methylation of histone H3 lysine 9 (H3K9me) and its binding protein Swi6/HP1 localizes at the telomere, centromere, and mating-type loci. These loci contain DNA sequences called <i>dg</i> and <i>dh</i>, and the RNA interference (RNAi)-dependent system establishes and maintains heterochromatin at <i>dg/dh</i>. Bi-directional transcription at <i>dg/dh</i> induced by RNA polymerase II is critical in RNAi-dependent heterochromatin formation because the transcribed RNAs provide substrates for siRNA synthesis and a platform for assembling RNAi factors. However, a regulator of <i>dg/dh</i> transcription during the establishment of heterochromatin is not known. Here, we found that a zinc-finger protein Moc3 localizes <i>dh</i> and activates <i>dh</i>-forward transcription in its zinc-finger-dependent manner when heterochromatin structure or heterochromatin-dependent silencing is compromised. However, Moc3 does not localize at normal heterochromatin and does not activate the <i>dh</i>-forward transcription. Notably, the loss of Moc3 caused a retarded heterochromatin establishment, showing that Moc3-dependent <i>dh</i>-forward transcription is critical for RNAi-dependent heterochromatin establishment. Therefore, Moc3 is a transcriptional activator that induces RNAi to establish heterochromatin.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 6","pages":"471-485"},"PeriodicalIF":2.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140614086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Clover: An unbiased method for prioritizing differentially expressed genes using a data-driven approach 三叶草使用数据驱动方法确定差异表达基因优先次序的无偏方法
IF 2.1 4区 生物学
Genes to Cells Pub Date : 2024-04-11 DOI: 10.1111/gtc.13119
Gina Miku Oba, Ryuichiro Nakato
{"title":"Clover: An unbiased method for prioritizing differentially expressed genes using a data-driven approach","authors":"Gina Miku Oba,&nbsp;Ryuichiro Nakato","doi":"10.1111/gtc.13119","DOIUrl":"10.1111/gtc.13119","url":null,"abstract":"<p>Identifying key genes from a list of differentially expressed genes (DEGs) is a critical step in transcriptome analysis. However, current methods, including Gene Ontology analysis and manual annotation, essentially rely on existing knowledge, which is highly biased depending on the extent of the literature. As a result, understudied genes, some of which may be associated with important molecular mechanisms, are often ignored or remain obscure. To address this problem, we propose Clover, a data-driven scoring method to specifically highlight understudied genes. Clover aims to prioritize genes associated with important molecular mechanisms by integrating three metrics: the likelihood of appearing in the DEG list, tissue specificity, and number of publications. We applied Clover to Alzheimer's disease data and confirmed that it successfully detected known associated genes. Moreover, Clover effectively prioritized understudied but potentially druggable genes. Overall, our method offers a novel approach to gene characterization and has the potential to expand our understanding of gene functions. Clover is an open-source software written in Python3 and available on GitHub at https://github.com/G708/Clover.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 6","pages":"456-470"},"PeriodicalIF":2.1,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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