Ye Wang

Summary: The emergence of multiomic single-cell Hi-C (scHi-C) methods, which simultaneously profile chromatin conformation and other modalities such as gene expression or DNA methylation, creates tremendous opportunities for studying the genome’s structure-function relationships. Existing tools for processing multiomic scHi-C datasets lack certain key functions for downstream bioinformatics analysis. We present map3C, a software tool that incorporates additional key functions. Specifically, we demonstrate that map3C facilitates multiomic scHi-C processing, quality control, and identification of structural variant locations in the genome. Availability and implementation: map3C is available at https://github.com/luogenomics/map3C and is archived at https://doi.org/10.5281/zenodo.20724719.

Summary: The emergence of multiomic single-cell Hi-C methods, which simultaneously profile chromatin conformation and other modalities such as gene expression or DNA methylation, creates tremendous opportunities for studying the genome’s structure-function relationships. Existing tools for processing multiomic single-cell Hi-C datasets have certain limitations for downstream bioinformatics analysis. We present map3C, a software tool designed to address these limitations. We demonstrate that map3C improves the quality of multiomic single-cell Hi-C data for analysis and its utility for identifying structural variant locations in the genome.

Platinum (Pt) drugs are widely utilized in cancer chemotherapy. Although cytotoxic and resistance mechanisms of Pt drugs have been thoroughly explored, it remains elusive what factors affect the receptiveness of DNA to drug-induced damage in nuclei. Here, we demonstrate that nuclear locations of chromatin play a key role in Pt drug-induced DNA damage susceptibility in vivo. By integrating data from damage-seq experiments with 3D genome structure information, we show that nuclear locations of chromatin relative to specific nuclear bodies and compartments explain patterns of cisplatin DNA damage susceptibility. This aligns with observations of cisplatin enrichment in biomolecular condensates at certain nuclear bodies. Finally, 3D structure mapping of DNA damage reveals characteristic differences between nuclear distributions of oxaliplatin-induced DNA damage in drug resistant versus sensitive cells. DNA damage increases in gene-poor chromatin at the nuclear periphery, while it decreases in gene-rich regions located at nuclear speckles. This suggests a strategic redistribution of Pt drug-induced damage in nuclei during chemoresistance development.

RNA modification C²-methyladenosine (m²A) exists in both rRNA and tRNA of Escherichia coli (E. coli), installed by the methyltransferase RlmN using a radical-S-adenosylmethionine (SAM) mechanism. However, the precise function of m²A in tRNA and its ubiquity in plants have remained unclear. Here we discover the presence of m²A in chloroplast rRNA and tRNA, as well as cytosolic tRNA, in multiple plant species. We identify six m²A-modified chloroplast tRNAs and two m²A-modified cytosolic tRNAs across different plants. Furthermore, we characterize three Arabidopsis m²A methyltransferases—RLMNL1, RLMNL2, and RLMNL3—which methylate chloroplast rRNA, chloroplast tRNA, and cytosolic tRNA, respectively. Our findings demonstrate that m²A37 promotes a relaxed conformation of tRNA, enhancing translation efficiency in chloroplast and cytosol by facilitating decoding of tandem m²A-tRNA-dependent codons. This study provides insights into the molecular function and biological significance of m²A, uncovering a layer of translation regulation in plants.

N6-methyladenosine (m6A) is a common transcriptomic modification in cancer. Recently, it has been found to be involved in the regulation of non-small cell lung cancer (NSCLC) formation and metastasis. Interleukin 37 (IL-37) plays a crucial protective role in lung cancer. In our previous studies, we found that IL-37 is a potential novel tumor suppressor by inhibiting IL-6 expression to suppress STAT3 activation and decreasing epithelial-to-mesenchymal transition. Moreover, we found that treatment of IL-37 in lung cancer cells induced widespread and dynamic RNA m6A methylation. The effects of RNA m6A methylation of IL-37 treatment require further study. However, the functions of RNA m6A methylation of IL-37 treatment still await elucidation. Using MeRIP-seq and RNA-seq, we uncovered a unique m6A methylation profile in the treatment of IL-37 on the A549 cell line. We also showed the expression of m6A writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO in A549 cells and lung cancer tissues after the treatment of IL-37. This study showed that IL-37 could lead to changes in m6A methylation level and related molecule expression level in A546 cells and may downregulate the proliferation by inhibiting Wnt5a/5b pathway in A549 cells. We conclude that IL-37 suppresses tumor growth through regulation of RNA m6A methylation in lung cancer cells.

N⁶-methyladenosine (m⁶A) is the most abundant modification of eukaryotic mRNA. Although m⁶A has been demonstrated to affect almost all aspects of RNA metabolism, its global contribution to the post-transcriptional balancing of translational efficiency remains elusive in plants. In this study, we performed a parallel analysis of the transcriptome-wide mRNA m⁶A distribution and polysome profiling in two maize (Zea mays) inbred lines to assess the global correlation of m⁶A modification with translational status. m⁶A sites are widely distributed in thousands of protein-coding genes, confined to a consensus motif and primarily enriched in the 3′ untranslated regions, and highly coordinated with alternative polyadenylation usage, suggesting a role of m⁶A modification in regulating alternative polyadenylation site choice. More importantly, we identified that the m⁶A modification shows multifaceted correlations with the translational status depending on its strength and genic location. Moreover, we observed a substantial intraspecies variation in m⁶A modification, and this natural variation was shown to be partly driven by gene-specific expression and alternative splicing. Together, these findings provide an invaluable resource for ascertaining transcripts that are subject to m⁶A modification in maize and pave the way to a better understanding of natural m⁶A variation in mediating gene expression regulation.

The inert chemical property of RNA modification N ⁶ -methyladenosine (m ⁶ A) makes it very challenging to detect, and all of the transcriptome-wide m ⁶ A detection methods rely on m ⁶ A-antibody immunoprecipitation. However, their results are dependent on the quality and specificity of antibodies. Although the endoribonuclease-based single-base m ⁶ A sequencing is antibody-free, it maps only 16~25% sites. Here, we present an antibody-free, FTO-assisted chemical labeling method termed m ⁶ A-SEAL for m ⁶ A detection. We applied m ⁶ A-SEAL to profile m ⁶ A landscapes in human and plant, which had good overlaps with antibody-based results and displayed the known m ⁶ A distribution features in transcriptome. Comparison with all available m ⁶ A sequencing methods and specific m ⁶ A sites validation by SELECT, we demonstrated that m ⁶ A-SEAL has good sensitivity, specificity, and reliability for transcriptome-wide detection of m ⁶ A. Given its tagging ability and FTO’s oxidation property, m ⁶ A-SEAL enables many applications like enrichment, imaging, and sequencing techniques to drive future functional studies of m ⁶ A and other modifications.

A simple improved mix-and-read method for the detection of bacteria is developed based on a DNAzyme and a molecular beacon.

N6-methyldeoxyadenine (6mA), a major type of DNA methylation in bacteria, represents a part of restriction-modification systems to discriminate host genome from invader DNA1. With the recent advent of more sensitive detection techniques, 6mA has also been detected in some eukaryotes2-8. However, the physiological function of this epigenetic mark in eukaryotes remains elusive. Heritable changes in DNA 5mC methylation have been associated with transgenerational inheritance of responses to a high-fat diet9, thus raising the exciting possibility that 6mA may also be transmitted across generations and serve as a carrier of inheritable information. Using Caenorhabditis elegans as a model, here we report that histone H3K4me3 and DNA 6mA modifications are required for the transmission of mitochondrial stress adaptations to progeny. Intriguingly, the global DNA 6mA level is significantly elevated following mitochondrial perturbation. N6-methyldeoxyadenine marks mitochondrial stress response genes and promotes their transcription to alleviate mitochondrial stress in progeny. These findings suggest that 6mA is a precisely regulated epigenetic mark that modulates stress response and signals transgenerational inheritance in C. elegans.