Biology subjects

Israel, E.

Publications and source records attributed to Israel, E..

4 recordsLinked to original sources

bioRxiv2025

MBD2/3 lost its methyl-CpG binding ability in multiple families of Holometabola

DNA methylation is sparse in insects, compared to vertebrates. This reduction is even more pronounced in Holometabola, where the loss of DNA methyltransferases DNMT1 and DNMT3 has occurred several times. In some Holometabola, DNA methylation is lost entirely. Methyl-CpG-binding domain (MBD) proteins bind methylated CpGs and are therefore important readers of these epigenetic marks. We hypothesize that the evolutionary reduction of genome-wide methylation may be paralleled by changes to MBD proteins. Among insects, only a single MBD family member, MBD2/3, is known. Two isoforms of MBD2/3 have been identified in Bombyx mori, MBD2/3-L and MBD2/3-S. The long isoform MBD2/3-L contains a complete MBD domain spanning the first two exons, whereas the short isoform MBD2/3-S lacks the second exon and therefore half of its MBD domain. It has been reported that only the MBD2/3-L isoform is able to bind methyl-CpGs. In this study, we analyzed transcriptomic and genomic sequence data across holometabolous orders to identify MBD2/3 genes and their isoforms. Our findings reveal that MBD2/3 is highly conserved in sequence and gene structure. While both isoforms are present in most hemimetabolous orders, the long isoform MBD2/3-L, capable of binding methylated CpG, has been lost in multiple holometabolous orders. The results suggest that MBD2/3 has lost its ability to bind methyl-CpG in several insect orders, with several independent losses in Holometabola. This occurred through different changes to the MBD domain, from sequence divergence within the domain to the absence of half of the MBD domain. These losses may be linked to the reduced levels of CpG DNA methylation.

bioinformatics↗

bioRxiv2025

Telomerase RNA gene duplications drive telomeric repeatdiversity and evolution in Andrena bees

Most organisms in the animal kingdom require a non-coding telomerease RNA (TR) in conjunction with the telomerase reverse transcriptase (TERT) to add telomere tandem repeats to chromosome ends to genomic instability. Recent studies reported an extensive diversity in the sequence of telomeric repeats in some insect species. Our investigation of TR genes in the Andrena genus provides convincing evidence for the presence of multiple TR gene copies with different template sequences for synthesis of distinct telomeric repeat sequences in several species. In this study we describe the structure, genomic coordinates and abundance of these TR genes, and correlate our findings with the levels of tandem repeats found in DNAseq data. Based on an analysis of the synthenic context of these newly predicted TR genes, we show evidence for the existence of multiple TR paralogs that diverged during the evolution of the genus Andrena. To our knowledge this is the first time such a phenomenon is observed in animals, although recently reported for plants. Interestingly, the comprehensive annotation of all TERT genes found in yet unannotated Andrena species shows no corresponding evolutionary changes in related TERT proteins encoded by a single copy gene. Our study suggests an evolutionary mechanism for diversification of telomeric repeat sequences in certain insect species through telomerase RNA gene duplication.

bioinformatics↗

bioRxiv2025

Multiomics reveal associations between CpG methylation, histone modifications and transcription in a species that has lost DNMT3, the Colorado potato beetle

Insects display exceptional phenotypic plasticity, which can be mediated by epigenetic modifications, including CpG methylation and histone modifications. In vertebrates, both are interlinked and CpG methylation is associated with gene repression. However, little is known about these regulatory systems in invertebrates, where CpG methylation is mainly restricted to gene bodies of transcriptionally active genes. A widely conserved mechanism involves the co-transcriptional deposition of H3K36 trimethylation and the targeted methylation of unmethylated CpGs by the de novo DNA methyltransferase DNMT3. However, DNMT3 has been lost multiple times in invertebrate lineages raising the question of how the links between CpG methylation, histone modifications and gene expression are affected by its loss. Here, we report the epigenetic landscape of Leptinotarsa decemlineata, a beetle species that has lost DNMT3 but retained CpG methylation. We combine RNA-seq, enzymatic methyl-seq and CUT&Tag to study CpG methylation and patterns of H3K36me3 and H3K27ac histone modifications on a genome-wide scale. Despite the loss of DNMT3, H3K36me3 mirrors CpG methylation patterns. Together, they give rise to signature profiles for expressed and non-expressed genes. H3K27ac patterns, which show no association with CpG methylation, have a prominent peak at the transcription start site that is predictive of expressed genes. Our study provides new insights into the evolutionary flexibility of epigenetic modification systems that urge caution when generalizing across species. Research highlightsDespite lacking DNMT3, EM-seq revealed CpG methylation in the Colorado potato beetle. CUT&Tag showed an association of H3K36me3 and H3K27ac with transcription, while only H3K36me3 aligns with CpG methylation, demonstrating epigenetic flexibility.

evolutionary biology↗

bioRxiv2024

An Adipo-Pulmonary Axis Mediated by FABP4 Hormone Defines a Therapeutic Target Against Obesity-Induced Airway Disease

Obesity-related airway disease is a clinical condition without a clear description and effective treatment. Here, we define this pathology and its unique properties, which differ from classic asthma phenotypes, and identify a novel adipo-pulmonary axis mediated by FABP4 hormone as a critical mediator of obesity-induced airway disease. Through detailed analysis of murine models and human samples, we elucidate the dysregulated lipid metabolism and immunometabolic responses within obese lungs, particularly highlighting the stress response activation and downregulation of surfactant-related genes, notably SftpC. We demonstrate that FABP4 deficiency mitigates these alterations, demonstrating a key role in obesity-induced airway disease pathogenesis. Importantly, we identify adipose tissue as the source of FABP4 hormone in the bronchoalveolar space and describe strong regulation in the context of human obesity, particularly among women. Finally, our exploration of antibody-mediated targeting of circulating FABP4 unveils a novel therapeutic avenue, addressing a pressing unmet need in managing obesity-related airway disease. These findings not only define the presence of a critical adipo-pulmonary endocrine link but also present FABP4 as a therapeutic target for managing this unique airway disease that we refer to as fatty lung disease associated with obesity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=162 HEIGHT=200 SRC="FIGDIR/small/603433v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@c1449corg.highwire.dtl.DTLVardef@7f6869org.highwire.dtl.DTLVardef@9fd41corg.highwire.dtl.DTLVardef@11eb408_HPS_FORMAT_FIGEXP M_FIG C_FIG One Sentence SummaryInvestigating FABP4s pivotal role in obesity-driven airway disease, this study unveils an adipo-pulmonary axis with potential therapeutic implications.

physiology↗