Heterochromatin Regions Research Articles

SSR-маркеры, ассоциированные с геном-восстановителем ЦМС 9Е сорго

9E type of cytoplasmic male sterility (CMS) in sorghum belongs to environmentally-regulated types of male sterility in which the restoration of fertility is regulated, along with the genotype, by plant water availability and air humidity on the eve and during the flowering period. For studying the genetic control and understanding the mechanisms of epigenetic processes that regulate the restoration of fertility in this CMS type, the identification of fertility restoring genes (Rf-9E) is extremely important. To solve this problem, we carried out the work on identification of molecular markers associated with the Rf-9E genes. For this purpose, we used the plants of the BC1 population [(9E Pishchevoe 614 × 84/19) × Pishchevoe 614] segregated for fertility restoration. In total, 55 SSR markers were used, mapping all 10 chromosomes of the sorghum genome. It was found that SSR markers located on chromosome 2 of the sorghum genome, sam60498 (23911554…23913675 bp) and sam37585 (33055782…33056867 bp), demonstrate a significant association with the restoration of male fertility in the studied population. In silico analysis of the reference genome of S. bicolor (BTx623) showed that near this region, which includes more than 9 million bp, there are a pericentromeric heterochromatin region, and two PPR genes, 002G142700.1 and 002G144300.1 located at 23465796…23468350 bp and 23810047…23812824bp, respectively. Given that the vast majority of cloned Rf-genes in various plant species, including sorghum, contain sequences of PPR genes, the SSR markers identified in this study can indeed be the molecular markers of 9ECMS fertility-restoring genes. A hypothesis on the relationship between the localization of CMS 9E fertility-restoring genes near heterochromatin and the “moisture-dependent” nature of male fertility restoration in this CMS type is discussed.

Discovery of Potent Peptidomimetic Antagonists for Heterochromatin Protein 1 Family Proteins.

The heterochromatin protein 1 (HP1) sub-family of CBX chromodomains are responsible for the recognition of histone H3 lysine 9 tri-methyl (H3K9me3)-marked nucleosomal substrates through binding of the N-terminal chromodomain. These HP1 proteins, namely, CBX1 (HP1β), CBX3 (HP1γ), and CBX5 (HP1α), are commonly associated with regions of pericentric heterochromatin, but recent literature studies suggest that regulation by these proteins is likely more dynamic and includes other loci. Importantly, there are no chemical tools toward HP1 chromodomains to spatiotemporally explore the effects of HP1-mediated processes, underscoring the need for novel HP1 chemical probes. Here, we report the discovery of HP1 targeting peptidomimetic compounds, UNC7047 and UNC7560, and a biotinylated derivative tool compound, UNC7565. These compounds represent an important milestone, as they possess nanomolar affinity for the CBX5 chromodomain by isothermal titration calorimetry (ITC) and bind HP1-containing complexes in cell lysates. These chemical tools provide a starting point for further optimization and the study of CBX5-mediated processes.

Changes in the contour of karyology and histoarchitecture of the primary respiratory organ in the fish Oreochromis mossambicus (Peters, 1852) inhabiting the polluted estuarine ecosystem

The wetland ecosystem (WE) is subject to pollution by many anthropogenic activities, including domestic and industrial effluents. These effluents may contain toxic heavy metals that can interact within the aquatic ecosystem and have a capacity to disturb the metabolic activities, histological profile, and genetic structure and functions in aquatic species inhabiting the environment. The present study observed the karyological and histological alterations in gills of the freshwater fish, Mozambique tilapia, Oreochromis mossambicus in two different sublethal concentrations (1% and 3%) of heavy metals in 7, 15, and 30 days of experimental periods. The heavy metals induced various structural damages such as ring chromosome, sister chromatid exchange, acrocentric association region, condensed chromosomal morphology, heterochromatin region, and nucleolar organizer region in the chromosomes of O. mossambicus treated with 1% and 3% sublethal concentrations of water sample collected from Pallikaranai wetland ecosystem. Gills exposed to 1% and 3% effluent exhibited several variations in the respiratory surfaces of gill arches or lamellae in the light and scanning microscopical study. The gills exposed to 1% concentration for 30 days showed marked necrosis, and the secondary lamellae showed the lamellar membrane's dissolution. Exposure of gills to raw effluent in the field condition was observed in the presence of Cd, Pb, Cr, Cu, and Zn. Thus, this present study shows the environmental deterioration by heavy metal pollution on the structure of the gills in tilapia.

The World of Pseudogenes: New Diagnostic and Therapeutic Targets in Cancers or Still Mystery Molecules?

Pseudogenes were once considered as “junk DNA”, due to loss of their functions as a result of the accumulation of mutations, such as frameshift and presence of premature stop-codons and relocation of genes to inactive heterochromatin regions of the genome. Pseudogenes are divided into two large groups, processed and unprocessed, according to their primary structure and origin. Only 10% of all pseudogenes are transcribed into RNAs and participate in the regulation of parental gene expression at both transcriptional and translational levels through senseRNA (sRNA) and antisense RNA (asRNA). In this review, about 150 pseudogenes in the different types of cancers were analyzed. Part of these pseudogenes seem to be useful in molecular diagnostics and can be detected in various types of biological material including tissue as well as biological fluids (liquid biopsy) using different detection methods. The number of pseudogenes, as well as their function in the human genome, is still unknown. However, thanks to the development of various technologies and bioinformatic tools, it was revealed so far that pseudogenes are involved in the development and progression of certain diseases, especially in cancer.

Heterochromatin is a quantitative trait associated with spontaneous epiallele formation

Epialleles are meiotically heritable variations in expression states that are independent from changes in DNA sequence. Although they are common in plant genomes, their molecular origins are unknown. Here we show, using mutant and experimental populations, that epialleles in Arabidopsis thaliana that result from ectopic hypermethylation are due to feedback regulation of pathways that primarily function to maintain DNA methylation at heterochromatin. Perturbations to maintenance of heterochromatin methylation leads to feedback regulation of DNA methylation in genes. Using single base resolution methylomes from epigenetic recombinant inbred lines (epiRIL), we show that epiallelic variation is abundant in euchromatin, yet, associates with QTL primarily in heterochromatin regions. Mapping three-dimensional chromatin contacts shows that genes that are hotspots for ectopic hypermethylation have increases in contact frequencies with regions possessing H3K9me2. Altogether, these data show that feedback regulation of pathways that have evolved to maintain heterochromatin silencing leads to the origins of spontaneous hypermethylated epialleles.

EPCO-08. ATRX DEFICIENCY INDUCES DYSFUNCTIONAL HETEROCHROMATIN ARCHITECTURE IN GLIOMAS AND ESTABLISHES DISEASE-DEFINING TRANSCRIPTIONAL NETWORKS

Abstract Loss of ATRX (Alpha Thalassemia/Mental Retardation Syndrome X, a member of SWI/SNF family chromatin regulator is altered in diffuse gliomas and defines molecular subtypes with aggressive behavior. Mechanistically, ATRX regulates incorporation of histone H3.3 into chromatin sites across the genome, maintains alternative lengthening of telomeres and establishes genomic distribution of polycomb responsive genes. We have recently reported Atrx deficiency induces glioma oncogenic features via widespread alterations in chromatin accessibility using mouse Neural Progenitor Cells (mNPCs- Tp53 -/-,Atrx -/-). Surprisingly, Atrx was found to be associated with transcription start site and enhancer regions, suggesting their strong association with epigenome architecture. In this background, we have recently performed ChIP-seq for histone marks that define active transcription, enhancers, repressors and gene bodies and Cohesion molecules on Atrx intact and deficient mNPCs. Our integrated analysis reports depletion of H3K9me3 loci’s with enrichment of H3K27me3 marks that coincidently enriched with Atrx binding sites and Lamina-Associated Domains (LADs). GSEA confirmed that the genes corresponding to “newly formed LADs” in mNPC-to-astrocyte differentiation are significantly enriched for genes down-regulated in Atrx deficient mNPCs and belongs to Gene Ontology categories such as cell cycle, chromosome organization and DNA damage. Alternatively, genes corresponding to decreased LAD association are enriched for up-regulated genes in Atrx deficient mNPCs and for regulation of differentiation, adhesion and cell death. Additionally, whole-genome bisulphite sequencing further demonstrated loss of methylation marks at H3K9me3 sites in Atrx deficient mNPCs, suggesting perturbations of heterochromatin regions leading to activation of canonical signals that define glioma phenotype and disease-state. To summarize, our data establishes tangible links between Atrx deficiency and dysregulated chromatin and heterochromatin architecture in gliomas and suggests the role of Atrx in establishing global chromatin features and transcriptional networks. Further, our data unravel novel therapeutic molecules/pathways for engineering potential.

Chromosomal Differentiation of Deschampsia (Poaceae) Based on Four Satellite DNA Families.

Diverse families of satellite DNA (satDNA) were detected in heterochromatin regions of Deschampsia. This kind of repetitive DNA consists of tandem repeat sequences forming big arrays in genomes, and can contribute to lineages differentiation. The differentiation between types of satDNA is related to their sequence identity, the size and number of monomers forming the array, and their chromosomal location. In this work, four families of satDNA (D2, D3, D12, D13), previously isolated by genomic analysis, were studied on chromosomal preparations of 12 species of Deschampsia (D. airiformis, D. antarctica, D. cespitosa, D. cordillerarum, D. elongata, D. kingii, D. laxa, D. mendocina, D. parvula, D. patula, D. venustula, and Deschampsia sp) and one of Deyeuxia (D. eminens). Despite the number of satDNA loci showing interspecific variation, the general distribution pattern of each satDNA family is maintained. The four satDNA families are AT-rich and associated with DAPI + heterochromatin regions. D2, D3, and D12 have mainly subterminal distribution, while D13 is distributed in intercalary regions. Such conservation of satDNA patterns suggests a not random distribution in genomes, where the variation between species is mainly associated with the array size and the loci number. The presence of satDNA in all species studied suggests a low genetic differentiation of sequences. On the other hand, the variation of the distribution pattern of satDNA has no clear association with phylogeny. This may be related to high differential amplification and contraction of sequences between lineages, as explained by the library model.

Anadolu’ya endemik Squalius anatolicus (Bogutskaya, 1997) (Teleostei, Leuciscidae) türünün karyotip, C-bant ve NOR fenotipi

The karyotype and distribution of constitutive heterochromatin and nucleolus organizer regions (NORs) of Anatolian leuciscine endemic to Lake Beysehir, Squalius anatolicus (Bogutskaya, 1997) were analyzed respectively using conventional Giemsa-staining, C-banding and Ag-impregnation. Diploid chromosome number was 2n = 50 and karyotype consisted of 7 pairs of metacentric, 13 pairs of submetacentric, 5 pairs of subtelo- to acrocentric chromosomes, NF value equaled 90. Heteromorphic elements indicating sex chromosomes were not detected. C-banding revealed clear pericentromeric constitutive heterochromatin blocks in several chromosomes. Ag-impregnation revealed the size heteromorphism of NORs that covered almost the entire short arms of the middle-sized submetacentric chromosome pair. The karyotype pattern and simple NOR phenotype of S. anatolicus are nearly identical with that found not only in Squalius species analyzed to date but also in many other representatives of the Eurasian leuciscine cyprinids, which indicates remarkable chromosome stasis in this leuciscid lineage.

Parent-of-origin effects on nuclear chromatin organization and behavior in a Drosophila model for Williams–Beuren Syndrome

Prognosis of neuropsychiatric disorders in progeny requires consideration of individual (1) parent-of-origin effects (POEs) relying on (2) the nerve cell nuclear 3D chromatin architecture and (3) impact of parent-specific miRNAs. Additionally, the shaping of cognitive phenotypes in parents depends on both learning acquisition and forgetting, or memory erasure. These processes are independent and controlled by different signal cascades: the first is cAMPdependent, the second relies on actin remodeling by small GTPase Rac1 – LIMK1 (LIM-kinase 1). Simple experimental model systems such as Drosophila help probe the causes and consequences leading to human neurocognitive pathologies. Recently, we have developed a Drosophila model for Williams–Beuren Syndrome (WBS): a mutant agnts3 of the agnostic locus (X:11AB) harboring the dlimk1 gene. The agnts3 mutation drastically increases the frequency of ectopic contacts (FEC) in specific regions of intercalary heterochromatin, suppresses learning/memory and affects locomotion. As is shown in this study, the polytene X chromosome bands in reciprocal hybrids between agnts3 and the wild type strain Berlin are heterogeneous in modes of FEC regulation depending either on maternal or paternal gene origin. Bioinformatic analysis reveals that FEC between X:11AB and the other X chromosome bands correlates with the occurrence of short (~30 bp) identical DNA fragments partly homologous to Drosophila 372-bp satellite DNA repeat. Although learning acquisition in a conditioned courtship suppression paradigm is similar in hybrids, the middle-term memory formation shows patroclinic inheritance. Seemingly, this depends on changes in miR-974 expression. Several parameters of locomotion demonstrate heterosis. Our data indicate that the agnts3 locus is capable of trans-regulating gene activity via POEs on the chromatin nuclear organization, thereby affecting behavior.

Identification of regions of constitutive heterochromatin and sites of ribosomal DNA (rDNA) in Rhogeessa hussoni (Genoways & Baker, 1996) (Chiroptera; Mammalia; Vespertilionidae)

There is scarce information about the geographical distribution, biological and cytogenetic data from the Rhogeessa hussoni. This study aims to characterize its chromosome composition through chromosome bandings to visualize regions of constitutive heterochromatin (CGB bands) and sites of ribosomal DNA (rDNA) in R. hussoni’s karyotype. A female specimen of R. hussoni was collected in the “Parque Municipal Mário Viana” Conservation Unit, Nova Xavantina, Mato Grosso, Central-West region of Brazil. The karyotype constitution was 2n=52 and NF=54. The CBG bands evidenced a sex X chromosome nearly completely constituted by heterochromatin. The Rhogeessa hussoni has two sites of rDNA located in a single pair (pair 25) of autosomal chromosomes. We carried out the first cytogenetic characterization of R. hussoni, supplementing knowledge about regions of heterochromatin and ribosomal DNA in this species, thus contributing to future elucidations about the genetic diversification in the genus Rogheessa.

AI for the collective analysis of a massive number of genome sequences: various examples from the small genome of pandemic SARS-CoV-2 to the human genome.

In genetics and related fields, huge amounts of data, such as genome sequences, are accumulating, and the use of artificial intelligence (AI) suitable for big data analysis has become increasingly important. Unsupervised AI that can reveal novel knowledge from big data without prior knowledge or particular models is highly desirable for analyses of genome sequences, particularly for obtaining unexpected insights. We have developed a batch-learning self-organizing map (BLSOM) for oligonucleotide compositions that can reveal various novel genome characteristics. Here, we explain the data mining by the BLSOM: an unsupervised AI. As a specific target, we first selected SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) because a large number of viral genome sequences have been accumulated via worldwide efforts. We analyzed more than 0.6 million sequences collected primarily in the first year of the pandemic. BLSOMs for short oligonucleotides (e.g., 4-6-mers) allowed separation into known clades, but longer oligonucleotides further increased the separation ability and revealed subgrouping within known clades. In the case of 15-mers, there is mostly one copy in the genome; thus, 15-mers that appeared after the epidemic started could be connected to mutations, and the BLSOM for 15-mers revealed the mutations that contributed to separation into known clades and their subgroups. After introducing the detailed methodological strategies, we explain BLSOMs for various topics, such as the tetranucleotide BLSOM for over 5 million 5-kb fragment sequences derived from almost all microorganisms currently available and its use in metagenome studies. We also explain BLSOMs for various eukaryotes, including fishes, frogs and Drosophila species, and found a high separation ability among closely related species. When analyzing the human genome, we found enrichments in transcription factor-binding sequences in centromeric and pericentromeric heterochromatin regions. The tDNAs (tRNA genes) could be separated according to their corresponding amino acid.

Genome-wide mapping reveals R-loops associated with centromeric repeats in maize.

R-loops are stable chromatin structures comprising a DNA:RNA hybrid and a displaced single-stranded DNA. R-loops have been implicated in gene expression and chromatin structure, as well as in replication blocks and genome instability. Here, we conducted a genome-wide identification of R-loops and identified more than 700,000 R-loop peaks in the maize (Zea mays) genome. We found that sense R-loops were mainly enriched in promoters and transcription termination sites and relatively less enriched in gene bodies, which is different from the main gene-body localization of sense R-loops in Arabidopsis and Oryza sativa. At the chromosome scale, maize R-loops were enriched in pericentromeric heterochromatin regions, and a significant portion of R-loops were derived from transposable elements. In centromeres, R-loops preferentially formed within the binding regions of the centromere-specific histone CENH3, and centromeric retrotransposons were strongly associated with R-loop formation. Furthermore, centromeric retrotransposon R-loops were observed by applying the single-molecule imaging technique of atomic force microscopy. These findings elucidate the fundamental character of R-loops in the maize genome and reveal the potential role of R-loops in centromeres.

Genome-wide profiles of UV lesion susceptibility, repair, and mutagenic potential in melanoma.

Exposure to the ultraviolet (UV) radiation in sunlight creates DNA lesions, which if left unrepaired can induce mutations and contribute to skin cancer. The two most common UV-induced DNA lesions are the cis-syn cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), both of which can initiate mutations. Interestingly, mutation frequency across the genomes of many cancers is heterogenous with significant increases in heterochromatin. Corresponding increases in UV lesion susceptibility and decreases in repair are observed in heterochromatin versus euchromatin. However, the individual contributions of CPDs and 6-4PPs to mutagenesis have not been systematically examined in specific genomic and epigenomic contexts. In this study, we compared genome-wide maps of 6-4PP and CPD lesion abundances in primary cells and conducted comprehensive analyses to determine the genetic and epigenetic features associated with susceptibility. Overall, we found a high degree of similarity between 6-4PP and CPD formation, with an enrichment of both in heterochromatin regions. However, when examining the relative levels of the two UV lesions, we found that bivalent and Polycomb-repressed chromatin states were uniquely more susceptible to 6-4PPs. Interestingly, when comparing UV susceptibility and repair with melanoma mutation frequency in these regions, disparate patterns were observed in that susceptibility was not always inversely associated with repair and mutation frequency. Functional enrichment analysis hint at mechanisms of negative selection for these regions that are essential for cell viability, immune function and induce cell death when mutated. Ultimately, these results reveal both the similarities and differences between UV-induced lesions that contribute to melanoma.

Karyotype Differentiation Characterized by C-banded Heterochromatin and Nucleolus Organizer Regions in Anemonefish (Pomacentridae)

Karyotype Differentiation Characterized by C-banded Heterochromatin and Nucleolus Organizer Regions in Anemonefish (Pomacentridae)

Quadruplex Folding Promotes the Condensation of Linker Histones and DNAs via Liquid-Liquid Phase Separation.

Liquid-liquid phase separation (LLPS) of proteins and DNA has recently emerged as a possible mechanism underlying the dynamic organization of chromatin. We herein report the role of DNA quadruplex folding in liquid droplet formation via LLPS induced by interactions between DNA and linker histone H1 (H1), a key regulator of chromatin organization. Fluidity measurements inside the droplets, binding assays using G-quadruplex-selective probes, and structural analyses based on circular dichroism demonstrated that quadruplex DNA structures, such as the G-quadruplex and i-motif, promote droplet formation with H1 and decrease molecular motility within droplets. The dissolution of the droplets in the presence of additives and the LLPS of the DNA structural units indicated that, in addition to electrostatic interactions between the DNA and the intrinsically disordered region of H1, π-π stacking between quadruplex DNAs could potentially drive droplet formation, unlike in the electrostatically driven LLPS of duplex DNA and H1. According to phase diagrams of anionic molecules with various conformations, the high LLPS ability associated with quadruplex folding arises from the formation of interfaces consisting of organized planes of guanine bases and the side surfaces with a high charge density. Given that DNA quadruplex structures are well-documented in heterochromatin regions, it is imperative to understand the role of DNA quadruplex folding in the context of intranuclear LLPS.

Chromatin accessibility profiling in Neurospora crassa reveals molecular features associated with accessible and inaccessible chromatin

BackgroundRegulation of chromatin accessibility and transcription are tightly coordinated processes. Studies in yeast and higher eukaryotes have described accessible chromatin regions, but little work has been done in filamentous fungi.ResultsHere we present a genome-scale characterization of accessible chromatin regions in Neurospora crassa, which revealed characteristic molecular features of accessible and inaccessible chromatin. We present experimental evidence of inaccessibility within heterochromatin regions in Neurospora, and we examine features of both accessible and inaccessible chromatin, including the presence of histone modifications, types of transcription, transcription factor binding, and relative nucleosome turnover rates. Chromatin accessibility is not strictly correlated with expression level. Accessible chromatin regions in the model filamentous fungus Neurospora are characterized the presence of H3K27 acetylation and commonly associated with pervasive non-coding transcription. Conversely, methylation of H3 lysine-36 catalyzed by ASH1 is correlated with inaccessible chromatin within promoter regions. Conclusions: In N. crassa, H3K27 acetylation is the most predictive histone modification for open chromatin. Conversely, our data show that H3K36 methylation is a key marker of inaccessible chromatin in gene-rich regions of the genome. Our data are consistent with an expanded role for H3K36 methylation in intergenic regions of filamentous fungi compared to the model yeasts, S. cerevisiae and S. pombe, which lack homologs of the ASH1 methyltransferase.

Potential functions of histone H3.3 lysine 56 acetylation in mammals

ABSTRACT H3K56 acetylation (H3K56Ac) was first identified in yeast and has recently been reported to play important roles in maintaining genomic stability, chromatin assembly, DNA replication, cell cycle progression and DNA repair. Although H3.1K56Ac has been relatively well studied, the function of H3.3K56Ac remains mostly unknown in mammals. In this study, we used H3.3K56Q and H3.3K56R mutants to study the possible function of H3.3K56 acetylation. The K-to-Q substitution mimics a constitutively acetylated lysine, while the K-to-R replacement mimics a constitutively unmodified lysine. We report that cell lines harbouring mutation of H3.3K56R exhibit increased cell death and dramatic morphology changes. Using a Tet-Off inducible system, we found an increased population of polyploid/aneuploid cells and decreased cell viability in H3.3K56R mutant cells. Consistent with these results, the H3.3K56R mutant had compromised H3.3 incorporation into several pericentric and centric heterochromatin regions we tested. Moreover, mass spectrometry analysis coupled with label-free quantification revealed that biological processes regulated by the H3.3-associating proteins, whose interaction with H3.3 was markedly increased by H3.3K56Q mutation but decreased by H3.3K56R mutation, include sister chromatid cohesion, mitotic nuclear division, and mitotic nuclear envelope disassembly. These results suggest that H3.3K56 acetylation is crucial for chromosome segregation and cell division in mammals.

The mutagenic impact of melphalan in multiple myeloma.

The introduction of whole genome and exome sequencing partnered with advanced bioinformatic pipelines has allowed the comprehensive characterization of mutational processes (i.e., mutational signatures) in individual cancer patients. Studies focusing on multiple myeloma have defined several mutational processes, including a recently identified mutational signature (called "SBS-MM1") directly caused by exposure to high-dose melphalan (i.e., autologous stem cell transplant). High-dose melphalan exposure increases both the overall and nonsynonymous mutational burden detected between diagnosis and relapse by ~10-20%. Nevertheless, most of these mutations are acquired within the heterochromatin and late-replicating regions, rarely involving key myeloma driver genes. In this review, we summarize key studies that made this discovery possible, and we discuss potential clinical implications.

FVE promotes RNA-directed DNA methylation by facilitating the association of RNA polymerase V with chromatin.

Association of RNA polymerase V (Pol V) with chromatin is a critical step for RNA- directed DNA methylation (RdDM) in plants. Although the methylated DNA-binding proteins SUVH2 and SUVH9 and the chromatin remodeler-containing complex DRD1-DMS3-RDM1 are known to be required for the association of Pol V with chromatin, the molecular mechanisms underlying the association of Pol V with different chromatin environments remain largely unknown. Here we found that SUVH9 interacts with FVE, a homolog of the mammalian retinoblastoma-associated protein, which has been previously identified as a shared subunit of the histone deacetylase complex and the polycomb-type histone H3K27 trimethyltransferase complex. We demonstrated that FVE facilitates the association of Pol V with chromatin and thus contributes to DNA methylation at a substantial subset of RdDM target loci. Compared with FVE-independent RdDM target loci, FVE-dependent RdDM target loci are more abundant in gene-rich chromosome arms than in pericentromeric heterochromatin regions. This study contributes to our understanding of how the association of Pol V with chromatin is regulated in different chromatin environments.

Cross-Predicting Essential Genes between Two Model Eukaryotic Species Using Machine Learning.

Experimental studies of Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular and cellular processes in metazoans at large. Since the publication of their genomes, functional genomic investigations have identified genes that are essential or non-essential for survival in each species. Recently, a range of features linked to gene essentiality have been inferred using a machine learning (ML)-based approach, allowing essentiality predictions within a species. Nevertheless, predictions between species are still elusive. Here, we undertake a comprehensive study using ML to discover and validate features of essential genes common to both C. elegans and D. melanogaster. We demonstrate that the cross-species prediction of gene essentiality is possible using a subset of features linked to nucleotide/protein sequences, protein orthology and subcellular localisation, single-cell RNA-seq, and histone methylation markers. Complementary analyses showed that essential genes are enriched for transcription and translation functions and are preferentially located away from heterochromatin regions of C. elegans and D. melanogaster chromosomes. The present work should enable the cross-prediction of essential genes between model and non-model metazoans.