Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Xu, X., Li, G., Li, C., Zhang, J., Wang, Q., Simmons, D. K., Chen, X., Wijesena, N., Zhu, W., Wang, Z., Wang, Z., Ju, B., Ci, W., Lu, X., Yu, D., Wang, Q., Aluru, N., Oliveri, P., Zhang, Y. E., Martindale, M. Q., & Liu, J. Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis. National Science Review, 6(5), (2019):993-1003, doi:10.1093/nsr/nwz064.Major evolutionary transitions are enigmas, and the most notable enigma is between invertebrates and vertebrates, with numerous spectacular innovations. To search for the molecular connections involved, we asked whether global epigenetic changes may offer a clue by surveying the inheritance and reprogramming of parental DNA methylation across metazoans. We focused on gametes and early embryos, where the methylomes are known to evolve divergently between fish and mammals. Here, we find that methylome reprogramming during embryogenesis occurs neither in pre-bilaterians such as cnidarians nor in protostomes such as insects, but clearly presents in deuterostomes such as echinoderms and invertebrate chordates, and then becomes more evident in vertebrates. Functional association analysis suggests that DNA methylation reprogramming is associated with development, reproduction and adaptive immunity for vertebrates, but not for invertebrates. Interestingly, the single HOX cluster of invertebrates maintains unmethylated status in all stages examined. In contrast, the multiple HOX clusters show dramatic dynamics of DNA methylation during vertebrate embryogenesis. Notably, the methylation dynamics of HOX clusters are associated with their spatiotemporal expression in mammals. Our study reveals that DNA methylation reprogramming has evolved dramatically during animal evolution, especially after the evolutionary transitions from invertebrates to vertebrates, and then to mammals.This work was supported by the National Key Research and Development Program of China (2018YFC1003303), the Strategic Priority Research Program of the CAS (XDB13040200), the National Natural Science Foundation of China (91519306, 31425015), the Youth Innovation Promotion Association of the CAS and the Key Research Program of Frontier Sciences, CAS (QYZDY-SSW-SMC016)

Infection with a Virulent Strain of Wolbachia Disrupts Genome Wide-Patterns of Cytosine Methylation in the Mosquito Aedes aegypti

BACKGROUND Cytosine methylation is one of several reversible epigenetic modifications of DNA that allow a greater flexibility in the relationship between genotype and phenotype. Methylation in the simplest models dampens gene expression by modifying regions of DNA critical for transcription factor binding. The capacity to methylate DNA is variable in the insects due to diverse histories of gene loss and duplication of DNA methylases. Mosquitoes like Drosophila melanogaster possess only a single methylase, DNMT2. DESCRIPTION Here we characterise the methylome of the mosquito Aedes aegypti and examine its relationship to transcription and test the effects of infection with a virulent strain of the endosymbiont Wolbachia on the stability of methylation patterns. CONCLUSION We see that methylation in the A. aegypti genome is associated with reduced transcription and is most common in the promoters of genes relating to regulation of transcription and metabolism. Similar gene classes are also methylated in aphids and honeybees, suggesting either conservation or convergence of methylation patterns. In addition to this evidence of evolutionary stability, we also show that infection with the virulent wMelPop Wolbachia strain induces additional methylation and demethylation events in the genome. While most of these changes seem random with respect to gene function and have no detected effect on transcription, there does appear to be enrichment of genes associated with membrane function. Given that Wolbachia lives within a membrane-bound vacuole of host origin and retains a large number of genes for transporting host amino acids, inorganic ions and ATP despite a severely reduced genome, these changes might represent an evolved strategy for manipulating the host environments for its own gain. Testing for a direct link between these methylation changes and expression, however, will require study across a broader range of developmental stages and tissues with methods that detect splice variants.This research was supported by The National Health and Medical Research Council of Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Epigenetic Mechanisms Governing Behavioral Reprogramming In The Ant Camponotus Floridanus

Eusocial insect colonies divide behaviors among specialist groups called castes. In some species, caste identity is determined by the interaction of endogenous (e.g. genomic) and exogenous (e.g. juvenile hormone from nurses) signals during larval development, suggesting epigenetic mechanisms underlie plastic traits tied to caste identity. Previous work demonstrated a link between patterns of histone H3 lysine 27 acetylation (H3K27ac) and caste-specific gene expression in Major and Minor workers of the ant Camponotus floridanus, and we hypothesized caste-specific behaviors such as foraging may be similarly regulated by histone acetylation. To test this hypothesis, we fed mature (~30d old) Majors and Minors with histone deacetylase inhibitors (HDACi), and CBP-dependent histone acetyl transferase inhibitors (HATi). We observed foraging enhancement after HDACi, and foraging suppression after HATi in Minors. Curiously, we did not observe increased foraging in HDACi treated mature (~30d) Majors. However, HDACi injections in callow (0-1d old) Majors succeeded in causing stable reprogramming of foraging behavior, indicating a critical period, or ‘window’ of epigenetic sensitivity to HDACi exists in young majors. To address this possibility, we injected Majors with HDACi in a time course and observed juvenile (d0-d5) Majors are susceptible to reprogramming, whereas mature (d10) Majors are not. To assess innate differences in the brain between castes, we conducted an RNA-seq study in untreated Major and Minor workers 0, 5, and 10 days old, and detected caste-specific patterns of juvenile hormone and ecdysone signaling. Finally, to characterize the transcriptional and epigenetic effects of reprogramming, we conducted RNA-seq in HDACi treated Major brains, and detected consistent upregulation of members of the neuron restrictive silencing factor (NRSF/REST) repressive complex (e.g. CoREST, RPD3, ttk). Notably, the top downregulated gene after HDACi is juvenile hormone esterase (JHe), which antagonizes JH signaling and inhibits foraging behavior in many eusocial insects. Thus, our results suggest REST/CoREST mediated repression of JHe may be a significant source of stable changes to foraging in behaviorally reprogrammed Majors

Predicting the Future: Parental Progeny Investment in Response to Environmental Stress Cues

Environmental stressors can severely limit the ability of an organism to reproduce as lifespan is decreased and resources are shifted away from reproduction to survival. Although this is often detrimental to the organism’s reproductive fitness, certain other reproductive stress responses may mitigate this effect by increasing the likelihood of progeny survival in the F1 and subsequent generations. Here we review three means by which these progeny may be conferred a competitive edge as a result of stress encountered in the parental generation: heritable epigenetic modifications to nucleotides and histones, simple maternal investments of cytosolic components, and the partially overlapping phenomenon of terminal investment, which can entail extreme parental investment strategies in either cytosolic components or gamete production. We examine instances of these categories and their ability to subsequently impact offspring fitness and reproduction. Ultimately, without impacting nucleotide sequence, these more labile alterations may shape development, evolution, ecology and even human health, necessitating further understanding and research into the specific mechanisms by which environmental stressors are sensed and elicit a corresponding response in the parental germline

The Emerging Role of Ten-Eleven Translocation 1 in Epigenetic Responses to Environmental Exposures.

Mounting evidence from epidemiological studies and animal models has linked exposures to environmental factors to changes in epigenetic markers, especially in DNA methylation. These epigenetic changes may lead to dysregulation of molecular processes and functions and mediate the impact of environmental exposures in complex diseases. However, detailed molecular events that result in epigenetic changes following exposures remain unclear. Here, we review the emerging evidence supporting a critical role of ten-eleven translocation 1 (TET1) in mediating these processes. Targeting TET1 and its associated pathways may have therapeutic potential in alleviating negative impacts of environmental exposures, preventing and treating exposure-related diseases

DNA demethylation by ROS1a in rice vegetative cells promotes methylation in sperm.

Epigenetic reprogramming is required for proper regulation of gene expression in eukaryotic organisms. In Arabidopsis, active DNA demethylation is crucial for seed viability, pollen function, and successful reproduction. The DEMETER (DME) DNA glycosylase initiates localized DNA demethylation in vegetative and central cells, so-called companion cells that are adjacent to sperm and egg gametes, respectively. In rice, the central cell genome displays local DNA hypomethylation, suggesting that active DNA demethylation also occurs in rice; however, the enzyme responsible for this process is unknown. One candidate is the rice REPRESSOR OF SILENCING 1a (ROS1a) gene, which is related to DME and is essential for rice seed viability and pollen function. Here, we report genome-wide analyses of DNA methylation in wild-type and ros1a mutant sperm and vegetative cells. We find that the rice vegetative cell genome is locally hypomethylated compared with sperm by a process that requires ROS1a activity. We show that many ROS1a target sequences in the vegetative cell are hypomethylated in the rice central cell, suggesting that ROS1a also demethylates the central cell genome. Similar to Arabidopsis, we show that sperm non-CG methylation is indirectly promoted by DNA demethylation in the vegetative cell. These results reveal that DNA glycosylase-mediated DNA demethylation processes are conserved in Arabidopsis and rice, plant species that diverged 150 million years ago. Finally, although global non-CG methylation levels of sperm and egg differ, the maternal and paternal embryo genomes show similar non-CG methylation levels, suggesting that rice gamete genomes undergo dynamic DNA methylation reprogramming after cell fusion

Strategies To Modulate Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature

Natural epigenetic processes precisely orchestrate the intricate gene network by expressing and suppressing genes at the right place and time, thereby playing an essential role in maintaining the cellular homeostasis. Environment-mediated alteration of this natural epigenomic pattern causes abnormal cell behavior and shifts the cell from the normal to a diseased state, leading to certain cancers and neurodegenerative disorders. Unlike heritable diseases that are caused by the irreversible mutations in DNA, epigenetic errors can be reversed. Inheritance of epigenetic memory is also a major concern in the clinical translation of the Nobel Prize-winning discovery of induced pluripotent stem cell technology. Consequently, there is an increasing interest in the development of novel epigenetic switch-based therapeutic strategies that could potentially restore the heritable changes in epigenetically inherited disorders. Here we give a comprehensive overview of epigenetic inheritance and suggest the prospects of therapeutic gene modulation using epigenetic-based drugs, in particular histone deacetylase inhibitors. This review suggests that there is a need to develop therapeutic strategies that effectively mimic the natural environment and include the ways to modulate the gene expression at both the genetic and epigenetic levels. The development of tailor-made small molecules that could epigenetically alter DNA in a sequence-specific manner is a promising approach for restoring defects in an altered epigenome and may offer a sustainable solution to some unresolved clinical issues