Plant Responses to Biotic Stress: Old Memories Matter

Plants are fascinating organisms present in most ecosystems and a model system for studying different facets of ecological interactions on Earth. In the environment, plants constantly encounter a multitude of abiotic and biotic stresses. The zero-avoidance phenomena make them more resilient to such environmental odds. Plants combat biotic stress or pathogenic ingression through a complex orchestration of intracellular signalling cascades. The plant–microbe interaction primarily relies on acquired immune response due to the absence of any specialised immunogenic cells for adaptive immune response. The generation of immune memory is mainly carried out by T cells as part of the humoral immune response in animals. Recently, prodigious advancements in our understanding of epigenetic regulations in plants invoke the “plant memory” theory afresh. Current innovations in cutting-edge genomic tools have revealed stress-associated genomic alterations and strengthened the idea of transgenerational memory in plants. In plants, stress signalling events are transferred as genomic imprints in successive generations, even without any stress. Such immunogenic priming of plants against biotic stresses is crucial for their eco-evolutionary success. However, there is limited literature capturing the current knowledge of the transgenerational memory of plants boosting biotic stress responses. In this context, the present review focuses on the general concept of memory in plants, recent advancements in this field and comprehensive implications in biotic stress tolerance with future perspectives.

Reproductive technologies, female infertility, and the risk of imprinting-related disorders

Background Epidemiological studies suggest that singletons born from assisted reproductive technologies (ART) have a high risk of adverse perinatal outcomes, specifically for imprinting disorders. Because ART processes take place at times when epigenetic reprogramming/imprinting are occurring, there is concern that ART can affect genomic imprints. However, little is currently known about the risk of imprinting defects according to the type of ART or the type of underlying female infertility. From the French national health database, a cohort of 3,501,495 singletons born over a 5-year period (2013–2017) following fresh embryo or frozen embryo transfers (fresh-ET or FET from in vitro fertilization), intrauterine insemination, or natural conception was followed up to early childhood. Based on clinical features, several syndromes/diseases involving imprinted genes were monitored. The effects of ART conception and the underlying cause of female infertility were assessed. Results Compared with infants conceived naturally, children born after fresh-ET had a higher prevalence of imprinting-related diseases, with an aOR of 1.43 [95% CI 1.13–1.81, p = 0.003]. Namely, we observed an increased risk of neonatal diabetes mellitus (1.96 aOR [95% CI 1.43–2.70], p < 0.001). There was an overall independent increase in risk of imprinting diseases for children with mothers diagnosed with endometriosis (1.38 aOR [95% CI 1.06–1.80], p = 0.02). Young and advanced maternal age, primiparity, obesity, smoking, and history of high blood pressure or diabetes were also associated with high global risk. Conclusions This prospective epidemiological study showed that the risk of clinically diagnosed imprinting-related diseases is increased in children conceived after fresh embryo transfers or from mothers with endometriosis. The increased perturbations in genomic imprinting could be caused by controlled ovarian hyperstimulation and potentially endometriosis through the impairment of endometrial receptivity and placentation, leading to epigenetic feto-placental changes. Further studies are now needed to improve understanding of the underlying molecular mechanisms (i.e. genetic or epigenetic causes).

Snowball Earths, population bottlenecks, and the evolution of marine photosynthetic bacteria

Prochlorococcus are the most abundant photosynthetic organisms in the modern ocean. A massive DNA loss event occurred in their early evolutionary history, leading to highly reduced genomes in nearly all lineages, as well as enhanced efficiency in both nutrient uptake and light absorption. The environmental landscape that shaped this ancient genome reduction, however, remained unknown. Through careful molecular clock analyses, we established that this Prochlorococcus genome reduction occurred during the Neoproterozoic Snowball Earth climate catastrophe. The lethally low temperature and exceedingly dim light during the Snowball Earth event would have inhibited Prochlorococcus growth and proliferation and caused severe population bottlenecks. These bottlenecks are recorded as an excess of deleterious mutations that accumulated across genomic regions in the descendant lineages. Prochlorococcus adaptation to extreme environmental conditions during Snowball Earth intervals can be inferred by tracing the evolutionary paths of genes that encode key metabolic potential. This metabolic potential includes modified lipopolysaccharide structure, strengthened peptidoglycan biosynthesis, the replacement of a sophisticated circadian clock with an hourglass-like mechanism that resets daily for dim light adaption, and the adoption of ammonia diffusion as an efficient membrane transporter-independent mode of nitrogen acquisition. In this way, the Neoproterozoic Snowball Earth event altered the physiological characters of Prochlorococcus, shaping their ecologically vital role as the most abundant primary producers in the modern oceans.Significance StatementProchlorococcus are the most abundant photosynthetic organisms in the modern ocean, where they support much of the marine and global biological productivity. In this study, we reconstructed a precise timeline of Prochlorococcus evolution and discovered that a major Prochlorococcus genome reduction took place during the Neoproterozoic Snowball Earth events. Since Prochlorococcus are generally adapted to warm waters, the extremely cold conditions during the Snowball Earth drove population bottlenecks, which left strong signatures in genomic DNA through the accumulation of detrimental mutations. The reconstruction of ancestral genome content further unveiled the metabolic strategies that Prochlorococcus evolved to overcome the extreme conditions during the climate catastrophe. These findings show how large changes in Earth’s past climate have left genomic imprints on extant microorganisms, likely shaping their metabolic potential and ecological role in the oceans today.

Basics and disturbances of genomic imprinting

Genomic imprinting ensures the parent-specific expression of either the maternal or the paternal allele, by different epigenetic processes (DNA methylation and histone modifications) that confer parent-specific marks (imprints) in the paternal and maternal germline, respectively. Most protein-coding imprinted genes are involved in embryonic growth, development, and behavior. They are usually organized in genomic domains that are regulated by differentially methylated regions (DMRs). Genomic imprints are erased in the primordial germ cells and then reset in a gene-specific manner according to the sex of the germline. The imprinted genes regulate and interact with other genes, consistent with the existence of an imprinted gene network. Defects of genomic imprinting result in syndromal imprinting disorders. To date a dozen congenital imprinting disorders are known. Usually, a given imprinting disorder can be caused by different types of defects, including point mutations, deletions/duplications, uniparental disomy, and epimutations. Causative trans-acting factors in imprinting disorders, including ZFP57 and the subcortical maternal complex (SCMC), have the potential to affect multiple DMRs across the genome, resulting in a multi-locus imprinting disturbance. There is evidence that mutations in components of the SCMC can confer an increased risk for imprinting disorders.

The pivotal roles of the NOD-like receptors with a PYD domain, NLRPs, in oocytes and early embryo development†

Nucleotide-binding oligomerization domain (NOD)-like receptors with a pyrin domain (PYD), NLRPs, are pattern recognition receptors, well recognized for their important roles in innate immunity and apoptosis. However, several NLRPs have received attention for their new, specialized roles as maternally contributed genes important in reproduction and embryo development. Several NLRPs have been shown to be specifically expressed in oocytes and preimplantation embryos. Interestingly, and in line with divergent functions, NLRP genes reveal a complex evolutionary divergence. The most pronounced difference is the human-specific NLRP7 gene, not identified in rodents. However, mouse models have been extensively used to study maternally contributed NLRPs. The NLRP2 and NLRP5 proteins are components of the subcortical maternal complex (SCMC), which was recently identified as essential for mouse preimplantation development. The SCMC integrates multiple proteins, including KHDC3L, NLRP5, TLE6, OOEP, NLRP2, and PADI6. The NLRP5 (also known as MATER) has been extensively studied. In humans, inactivating variants in specific NLRP genes in the mother are associated with distinct phenotypes in the offspring, such as biparental hydatidiform moles (BiHMs) and preterm birth. Maternal-effect recessive mutations in KHDC3L and NLRP5 (and NLRP7) are associated with reduced reproductive outcomes, BiHM, and broad multilocus imprinting perturbations. The precise mechanisms of NLRPs are unknown, but research strongly indicates their pivotal roles in the establishment of genomic imprints and post-zygotic methylation maintenance, among other processes. Challenges for the future include translations of findings from the mouse model into human contexts and implementation in therapies and clinical fertility management.

Epigenetic regulation of unique genes and repetitive elements by the KRAB zinc finger protein ZFP57

BackgroundKRAB-zinc finger proteins (KZFPs) represent one of the largest families of DNA binding proteins in vertebrate genomes and appear to have evolved to silence transposable elements (TEs) including endogenous retroviruses through sequence-specific targeting of repressive chromatin states. ZFP57 is required to maintain the post-fertilization DNA methylation memory of parental-origin at genomic imprints along with ZFP445 which is specific for imprints. However, ZFP57 has multiple methylated genomic targets. Here we conduct RNA-seq and ChIP-seq analyses in normal and ZFP57 mutant mouse ES cells to understand the relative importance of ZFP57 at unique and repetitive regions of the genome.ResultsOver 80% of ZFP57 targets are TEs, however, ZFP57 is not essential for their repression. The remaining targets lie within unique imprinted and non-imprinted sequences. Though loss of ZFP57 influences imprinted genes as expected, the majority of unique gene targets lose H3K9me3 with little effect on DNA methylation and very few exhibiting alterations in expression. Comparison with DNA methyltransferase-deleted ES cells (TKO) identifies remarkably similar losses of H3K9me3 and changes in expression, defining regions where H3K9me3 is secondary to DNA methylation. We show that ZFP57 is the principal methylation-sensitive KZFP recruiting KAP1 and H3K9me3 in ES cells. Finally, like imprints, other unique targets of ZFP57 are enriched for germline-derived DNA methylation including oocyte-specific methylation that is resistant to post-fertilisation epigenetic reprogramming.ConclusionOur analyses suggest the evolution of a rare DNA methylation-sensitive KZFP that is not essential for repeat silencing, but whose primary function is to maintain DNA methylation and repressive histone marks at germline derived imprinting control regions.

NLRPs, the subcortical maternal complex and genomic imprinting

Before activation of the embryonic genome, the oocyte provides many of the RNAs and proteins required for the epigenetic reprogramming and the transition to a totipotent state. Targeted disruption of a subset of oocyte-derived transcripts in mice results in early embryonic lethality and cleavage-stage embryonic arrest as highlighted by the members of the subcortical maternal complex (SCMC). Maternal-effect recessive mutations of NLRP7, KHDC3L and NLRP5 in humans are associated with variable reproductive outcomes, biparental hydatidiform moles (BiHM) and widespread multi-locus imprinting disturbances. The precise mechanism of action of these genes is unknown, but the maternal-effect phenomenon suggests a function during early pre-implantation development, while biochemical and genetic studies implement them as SCMC members or interacting partners. In this review article, we discuss the role of the NLRP family members and the SCMC proteins in the establishment of genomic imprints and post-zygotic methylation maintenance, the recent advances made in the understanding of the biology involved in BiHM formation and the wider roles of the SCMC in mammalian reproduction.