Genes & genetic systems最新文献

VANDAL family DNA transposons are prevalent in Arabidopsis and related plants. A notable feature of VANDALs is that they can overcome epigenetic silencing from the host, using a VANC protein encoded in each VANDAL member: VANC21 protein encoded in VANDAL21 specifically accumulates on its target DNA motifs that are concentrated in the non-coding regions of this TE and induces loss of DNA methylation, transcriptional derepression, and mobilization of the element. In this study, to elucidate the mechanism of how VANC subtypes have diverged to bind specifically to their own target motifs in their cognate VANDAL subfamilies, we determined the crystal structure of VANC21 in complex with its target DNA at 2.0 Å resolution. The VANC structure adopts a globular novel fold with a Zn ion coordinated at the DNA-binding site. Interestingly, most DNA-interacting VANC residues are located in the loops but not in the conserved regions among VANC subtypes. This observation suggests that the high variability of DNA-interacting regions of VANC proteins brought about the co-evolution of VANCs and their target sequences. This rapid differentiation by co-evolution enabled VANDAL family TEs to proliferate while avoiding deleterious effects on host fitness. Therefore, our findings help to understand the adaptive evolutionary strategy for the survival of parasitic sequences.

Ancient dispersal events from the Korean Peninsula to the Japanese main islands of Honshu, Shikoku and Kyushu (HSK), and from the Eurasian continent to Hokkaido via Sakhalin, have played a critical role in shaping the mammalian diversity of the Japanese archipelago. However, the timing and dynamics of these events remain incompletely understood across different taxa. In addition, the 100,000-year climatic cycles of glacial and interglacial periods during the Middle and Late Quaternary likely influenced intraspecific genetic diversity, although the mechanisms driving these changes remain unclear. In this study, we analyzed mitochondrial cytochrome b gene sequences from Japanese shrews (Sorex and Crocidura) and other small mammals from HSK and Hokkaido. Using an evolutionary rate of 0.029 substitutions/site/million years, we inferred that ancestral lineages of HSK species diverged during critical periods in the early Quaternary, such as around 2.4 and 1.7 million years ago (Ma), potentially in response to major climatic transitions. Notably, dispersal events of the Laxmann's shrew (S. caecutiens) and dark red-backed vole (Myodes rex) into Hokkaido around 1.7 Ma were also suggested. Regarding intraspecific mitochondrial DNA (mtDNA) lineages, species with broad distributions in HSK typically exhibit a north-south structure, characterized by two major lineages, as well as additional ancient lineages in surrounding offshore islands. Comparative analysis revealed that divergence among these lineages occurred at approximate intervals of 100,000 years. Our results indicate that the mtDNA genetic structure of HSK small mammals reflects geographic substructures shaped by climate-driven dispersal. Regions that facilitated rapid expansion during favorable climatic periods likely acted as centers of dispersal, from which haplotypes spread toward peripheral areas. As haplotypes radiated outward from these core regions, distinct mtDNA lineages became established across different geographic zones, giving rise to the spatial distribution patterns observed today.

Primula tibetica is an insect-pollinated, herbaceous, perennial plant belonging to the section Aleuritia (Primulaceae). The species exhibits the typical characteristics of heterostyly, with predominantly outcrossing populations comprising long-styled and short-styled floral morphs. Furthermore, significant variation occurs in floral morphology, categorised as homostyly, a phenomenon commonly associated with elevated selfing rates. Utilising next-generation sequencing, 25 microsatellite markers for P. tibetica were developed, with the objective of facilitating future investigations into the population genetics and mating patterns of the species. These markers were characterised by measuring polymorphism and genetic diversity in a sample of 36 individuals from three natural populations. The markers displayed relatively high polymorphism, with the number of observed alleles per locus ranging from two to 15 (mean = 7.26). The observed and expected heterozygosities ranged from 0.056 to 0.917 and 0.105 to 0.825, respectively. Furthermore, nineteen of these loci were also successfully amplified in P. pulchella. These microsatellite markers should serve as effective tools for investigating patterns of population genetic diversity and elucidating the evolutionary relationship between distyly and homostyly in P. tibetica.

In most eubacteria the initiator protein DnaA triggers chromosomal replication by forming an initiation complex at the origin of replication and also functions as a transcriptional regulator, coordinating gene expression with cell cycle progression. While genes regulated by DnaA are relatively well characterized in exponentially growing cells, its role in gene regulation during stationary phase remains insufficiently explored. Here, using the aquatic bacterium Caulobacter crescentus as a model, we show that C. crescentus DnaA (ccDnaA) acts as a repressor of the previously uncharacterized CCNA_00139 gene, which encodes a YifB family Mg chelatase-like AAA ATPase family protein of unknown function. Biochemical analyses reveal that ccDnaA forms multimers at this site, which may interfere with RNA polymerase access to the promoter by occupying overlapping binding sequences. Consistent with these findings, in exponentially growing C. crescentus cells the CCNA_00139 promoter is repressed in a ccDnaA-dependent manner. Notably, when cells enter stationary phase, CCNA_00139 promoter activity increases in parallel with ccDnaA clearance, supporting the idea that ccDnaA-mediated repression is relieved during this phase transition. Despite its regulated expression, deletion of CCNA_00139 did not result in any detectable growth, replication or DNA damage sensitivity phenotypes under the tested laboratory conditions, suggesting a possible role under specific environmental conditions. Given that this phase-dependent transcriptional switch may, in principle, apply to other uncharacterized ccDnaA-repressed genes, we infer that CCNA_00139, along with other such genes, form a regulatory network that supports quorum sensing or adaptation to growth phase transitions. We believe that these findings offer new insight into the potential role of bacterial DnaA in regulating gene expression in dormant or non-replicating cells across diverse bacterial species.

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.

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.

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 molecular pathogenesis of these diseases, with a particular focus on ICF syndrome and MLID.

DNA methylation is faithfully inherited during cell division, playing a crucial role in maintaining cellular identity. The process of DNA methylation maintenance relies on the 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-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.