Genes & genetic systems最新文献

{"title":"Molecular mechanisms of maintenance DNA methylation.","authors":"Christopher B Mulholland, Atsuya Nishiyama","doi":"10.1266/ggs.25-00073","DOIUrl":"https://doi.org/10.1266/ggs.25-00073","url":null,"abstract":"<p><p>Maintenance DNA methylation is essential for the stable inheritance of epigenetic information in vertebrates. While DNMT1 has long been recognized as the principal maintenance methyltransferase, recent studies have shown that its activity critically depends on ubiquitin signaling. Specifically, the E3 ligase UHRF1 enables DNMT1 recruitment and activation at hemimethylated sites through dual monoubiquitylation of both replication-associated and histone substrates. These insights have revised classical models of maintenance methylation and revealed new layers of regulation involving chromatin context, histone modifications, and nucleosome remodeling. In this review, we summarize the current understanding of the molecular mechanisms underlying DNMT1-mediated maintenance methylation, with a particular focus on ubiquitin-dependent pathways and their interplay with chromatin architecture.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626091","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}

{"title":"Development and characterization of expressed sequence tag-simple sequence repeat markers for the near-threatened halophyte Artemisia fukudo Makino.","authors":"Yoshikuni Hodoki, Kako Ohbayashi, Naoko Ishikawa, Yuka Inoki, Nonoka Takehara","doi":"10.1266/ggs.25-00033","DOIUrl":"https://doi.org/10.1266/ggs.25-00033","url":null,"abstract":"<p><p>RNA sequencing analysis was performed to develop 16 novel expressed sequence tag-simple sequence repeat (EST-SSR) markers to evaluate genetic variation in the near-threatened halophyte Artemisia fukudo Makino, which inhabits riversides and tidal muds affected by brackish water at high tide. In the four populations examined, the total number of alleles at each locus ranged from two to 13, with an average of 4.3. The observed and expected heterozygosity ranged from 0.05 to 0.64 and 0.06 to 0.72, respectively. These newly developed EST-SSR markers will support the understanding of the population genetic structure of A. fukudo and contribute to the conservation of this species.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600225","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}

{"title":"Biallelic genome engineering to create isogenic induced pluripotent stem cells modeling Huntington's disease.","authors":"Hikaru Kurasawa, Yuta Matsuura, Riho Yamane, Tomoyuki Ohno, Yasunori Aizawa","doi":"10.1266/ggs.25-00016","DOIUrl":"10.1266/ggs.25-00016","url":null,"abstract":"<p><p>We developed Huntington's disease (HD)-modeling induced pluripotent stem cells (iPSCs) by genome engineering of iPSCs from healthy donors. For this, we established a homologous-recombination-based biallelic substitution technique called the allele-specific universal knock-in system (asUKiS). asUKiS allows for scarless and allele-by-allele substitution of the entire region encompassing not only the polyQ repeat but also the associated genetic modifiers surrounding the repeat region, allowing us to generate five iPSC lines with identical genetic modifiers on both alleles, differing only in polyQ repeat numbers. All cell lines were validated by allele-specific genotyping to confirm the precise engineering of both alleles. Even for modeling autosomal dominant diseases, our approach of employing biallelic modification offers the distinct advantage of enabling investigation of the effects of specific genomic mutations with minimal interference from genetic background noise.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585440","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}

{"title":"Multiple Sry genes in the Okinawa spiny rat encode proteins with an A-to-S substitution in the HMG domain that retain DNA-binding ability.","authors":"Puntakarn Urunanont, Shusei Mizushima, Takeshi Uchida, Koichiro Ishimori, Luisa Matiz-Ceron, Asato Kuroiwa","doi":"10.1266/ggs.25-00021","DOIUrl":"10.1266/ggs.25-00021","url":null,"abstract":"<p><p>The mammalian sex-determining gene SRY is highly conserved across species, with only a few exceptions. The Japanese rodent genus Tokudaia is known for its unique sex chromosome evolution. The Okinawa spiny rat T. muenninki (TMU) acquired neo-sex chromosomes with multiple Sry copies by sex chromosome-autosome fusions. All SRY copies in TMU have a substitution from alanine to serine at position 21 in the high-mobility group (HMG) box, a critical DNA-binding domain, suggesting that they are nonfunctional. However, the sex determination system in TMU remains unclear, in part because the species is endangered and it is therefore extremely difficult to obtain experimental samples. In this study, we performed in silico and in vitro analyses to investigate the molecular properties and function of SRY using recently obtained whole-genome sequence and RNA-seq data. A comparison of SRY sequences from 225 species showed that TMU is the only species with a substitution at the 21st position. This result highlights the rarity and specificity of this substitution. Structural predictions, DNA docking simulations, electrophoretic mobility shift assays and fluorescence anisotropy showed that although the affinity was slightly lower than that of the mouse homolog, DNA-binding ability was retained. However, Sry expression was not detected in the testis, liver or brain in adult TMU. The complete absence of Sry expression in the adult tissues, despite an intact sequence, strongly indicates a loss of regulatory function. These findings provide insight into the unique evolution of the Sry gene in this species.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991816","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}

{"title":"Congenital diseases with defects in DNA methylation maintenance: Focusing on ICF syndrome and multilocus imprinting disturbance.","authors":"Motoko Unoki","doi":"10.1266/ggs.25-00045","DOIUrl":"https://doi.org/10.1266/ggs.25-00045","url":null,"abstract":"<p><p>DNA methylation is essential for transcriptional regulation and the maintenance of chromosome stability, and its precise inheritance upon DNA replication is indispensable for cellular homeostasis. The DNMT1/UHRF1 complex is critical in copying DNA methylation with accessory proteins, including CDCA7 and HELLS. The DNMT1/UHRF1 complex is also crucial for maintaining DNA methylation at imprinting control regions during preimplantation development against genome-wide DNA demethylation, an essential process for early embryos to acquire totipotency. Pathogenic variants in the genes involved in the mechanism of DNA methylation maintenance result in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, multilocus imprinting disturbance (MLID), autosomal dominant cerebellar ataxia-deafness and narcolepsy (ADCADN), neuropathy, hereditary sensory, type 1E (HSN1E), Kleefstra syndrome 1 (KLEFS1), and immunodeficiency 96 (IMD96). This review discusses recent progress in understanding the possible molecular pathogenesis of these diseases, with a particular focus on recent progress in understanding ICF syndrome and MLID.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274713","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}

{"title":"Involvement of Escherichia coli unconventional G protein, YchF, in cell growth at the stationary phase.","authors":"Yuto Kotaka, Takahiro Nagai, Kento Tominaga, Tatsuaki Kurata, Wataru Iwasaki, Yuko Nobe, Masato Taoka, Tsunaki Asano, Jun-Ichi Kato","doi":"10.1266/ggs.24-00218","DOIUrl":"10.1266/ggs.24-00218","url":null,"abstract":"<p><p>YchF is a universally conserved unconventional G protein. It is known to be involved in the translation of leaderless mRNA. However, leaderless mRNA is rare in Escherichia coli under normal culture conditions, so we analyzed E. coli YchF to clarify its function in vivo. First, bioinformatics analysis was performed, and then the growth and survival of ychF mutants were investigated. The results suggest that the functional domains and important amino acid residues of YchF are conserved. We next found that the ychF mutants exhibited delayed re-growth in late stationary phase in the presence of oxidative stress. Moreover, the growth inhibition by catalase overexpression was suggested to be caused by oxidase activity. We found that the E. coli ychF mutants exhibited reduced growth in early stationary phase that was associated with a decreased level of ribosomal 70S subunit. In the ychF mutants, we also found that overproduction of the ribosomal protein S18 inhibited growth, which was further suppressed by overproduction of S11. YchF of E. coli is involved in the regulation of ribosomal 70S levels possibly through interaction with ribosomal proteins S18 and S11 as well as IF-3, suggesting that YchF is important for growth and survival in the early and late stationary phase of growth.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700351","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}

{"title":"A Comprehensive Review of Structural Insights into DNA Methylation Maintenance.","authors":"Amika Kikuchi, Kyohei Arita","doi":"10.1266/ggs.25-00051","DOIUrl":"https://doi.org/10.1266/ggs.25-00051","url":null,"abstract":"<p><p>DNA methylation is faithfully inherited during cell division, playing a crucial role in maintaining cellular identity. The process of DNA methylation maintenance relies on DNA methyltransferase DNMT1 and the ubiquitin E3 ligase UHRF1. UHRF1 facilitates the ubiquitination of both the replication factor PAF15 and histone H3, with each ubiquitin signal regulating replication-coupled and uncoupled DNA methylation maintenance, respectively. Over the past decades, advances in structural biology have significantly deepened our understanding of the molecular mechanisms governing DNA methylation maintenance. In particular, the emergence of cryo-electron microscopy (cryo-EM)-often referred to as the \"Resolution Revolution\"-has transformed many areas of biology, including epigenetics and chromatin biology. This review focuses on the structural mechanisms of DNA methylation maintenance, as revealed by the three-dimensional structures of key biomolecular complexes and discusses the potential development of inhibitors targeting DNA methylation maintenance factors based on structural insights.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225198","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}

{"title":"Identification of candidate transcription factors that regulate Sox9 expression through the testis-specific enhancer in the Amami spiny rat (Tokudaia osimensis), an XO/XO mammal.","authors":"Shoichiro Mitsukawa, Shusei Mizushima, Yuki Kimura, Asato Kuroiwa","doi":"10.1266/ggs.25-00024","DOIUrl":"https://doi.org/10.1266/ggs.25-00024","url":null,"abstract":"<p><p>Testicular differentiation of undifferentiated gonads is generally triggered by the sex-determining region of chromosome Y (SRY/Sry) gene on the Y chromosome in most mammals. SRY and nuclear receptor subfamily 5, group A, member 1 (NR5A1) proteins regulate transcription of the autosomal SRY-box9 (SOX9/Sox9) gene in XY embryonic gonads, inducing testicular differentiation. One exception, the Amami spiny rat (Tokudaia osimensis), lacks the Y chromosome and Sry. We previously reported that this species has a male-specific duplication upstream of Sox9, and an enhancer (tosEnh14) in the duplication regulates Sox9 transcription without Sry. However, tosEnh14 is not activated by NR5A1 alone, suggesting another transcription factor(s) that binds to tosEnh14 is necessary. Although this species is endangered and heavily protected, it presents many challenges for genetic studies. Therefore, we explored novel transcription factors that regulate Sox9 via tosEnh14 using mouse samples. To detect proteins that bind to tosEnh14 DNA, Southwestern blotting analysis was performed using mouse embryonic gonad extracts. Bands of a similar molecular weight but prominent in males and faint in females were subjected to mass spectrometry analysis. Peptides derived from 174 genes were identified, and eight genes associated with gene ontology terms such as \"DNA binding\" and \"regulation of transcription by RNA polymerase II\" were selected. For further screening, the expression level of each gene was examined using single-cell RNA-sequencing data of mouse progenitor cells, which differentiate into Sertoli cells in mouse embryonic testes and granulosa cells in embryonic ovaries. Finally, five genes (Elf2, Etv6, Fiz1, Gtf2f1, and Trim27) whose expression was confirmed in seminiferous tubules of E13.5 XY embryos by whole-mount in situ hybridization were selected as candidates. Binding sites of ELF2 and ETV6 are present in tosEnh14 DNA sequence. Our study contributes to understanding of the molecular mechanisms underlying sex determination in mammals.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225200","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}

{"title":"Genetic Diversity and Population Structure of Cybister rugosus Based on the Mitochondrial COI Gene and Microsatellite Markers.","authors":"Fadel A Azhari, Etsuko Moritsuka, Ken-Ichi Odagiri, Junko Kusumi, Kunio Araya","doi":"10.1266/ggs.24-00131","DOIUrl":"https://doi.org/10.1266/ggs.24-00131","url":null,"abstract":"<p><p>The aquatic beetle Cybister rugosus has experienced ongoing habitat loss, a decline in population numbers, and confirmed extinctions among insular populations in Japan, it has recently been listed on the Red List as endangered by the Japanese Ministry of Environment and has been designated a specified class II nationally rare species of wild fauna and flora. To design effective conservation strategies for this species, it is essential to compile data on its genetic variation to ascertain its genetic diversity and population structure. However, studies on the COI gene revealed low levels of genetic variation among Japanese insular populations and failed to detect a fine population structure. Then, we developed ten novel microsatellite markers for C. rugosus, using whole genome shotgun sequencing. The degree of polymorphism for these markers was further characterized using summary statistics describing the genetic variation in 49 individuals from the populations in Cambodia and on the islands of the Ryukyu Archipelago. Microsatellite data indicated differentiation among the insular populations in Japan, which could not be clearly shown in the COI data, and some insular populations showed low levels of genetic diversity. The newly developed microsatellite markers will contribute to future ecological or evolutionary studies on this species and conservation research.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225199","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}

{"title":"Development of a TaqMan-based dosage analysis PCR assay for the molecular diagnosis of 22q11.2 deletion syndrome.","authors":"Dinali M Ranaweera, Deepthi C de Silva, Duminda Samarasinghe, Shehan Perera, Nirosha Kugalingam, Sumudu R Samarasinghe, Wadumesthri Y Madushani, Hiran H E Jayaweera, Siyath Gunewardene, Kajan Muneeswaran, Vaz S Gnanam, Naduviladath V Chandrasekharan","doi":"10.1266/ggs.24-00142","DOIUrl":"10.1266/ggs.24-00142","url":null,"abstract":"<p><p>A hemizygous 1.5-3.0-Mb microdeletion of human chromosome 22q11.2 with the loss of multiple genes including histone cell cycle regulator (HIRA) causes 22q11.2 deletion syndrome (22q11.2 DS), a common disorder with variable manifestations including congenital malformations affecting the heart, palate and kidneys in association with neurodevelopmental, psychiatric, endocrine and autoimmune abnormalities. The aim of this study was to develop a TaqMan-based dosage analysis PCR (TaqMan qPCR) for use as a rapid, cost-effective test for clinically suspected patients fulfilling previously described criteria for molecular diagnosis of 22q11.2 DS in a lower middle-income country where the cost of testing limits its use in routine clinical practice. Nineteen patients were recruited with informed consent following ethical approval from the Ethics Review Committee, Lady Ridgeway Hospital for Children, Colombo. Dosage analysis of extracted DNA was performed using a TaqMan qPCR assay by amplifying regions within the target (HIRA) and control (testin LIM domain protein (TES)) genes of suspected patient (P) and unaffected person (N) samples. For detection of a deletion, the normalized value (HIRA/TES dosage) of a P sample was compared with that of an N sample. A ratio of P:N of 0.5 confirmed the presence of a deletion while a ratio of 1.0 refuted this. Seven of the 19 patients were found to have a HIRA deletion, confirming the diagnosis of 22q11.2 DS, with these results being in complete agreement with those of fluorescence in situ hybridization (FISH) (performed in nine of the 19 cases) and whole-exome sequencing (all 19 samples tested). This TaqMan qPCR assay was able to reliably distinguish HIRA-deleted cases from non-deleted ones. The assay was both cheaper and faster compared to commercially available alternatives in our setting, including FISH and multiple ligation-dependent probe amplification.</p>","PeriodicalId":12690,"journal":{"name":"Genes & genetic systems","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023173","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}