Abstract Environmental stress from ultraviolet radiation, elevated temperatures or metal toxicity can lead to reactive oxygen species in cells, leading to oxidative DNA damage, premature aging, neurodegenerative diseases, and cancer. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activates many cytoprotective proteins within the nucleus to maintain homeostasis during oxidative stress. In vertebrates, Nrf2 levels are regulated by the Kelch-family protein Keap1 (Kelch-like ECH-associated protein 1) in the absence of stress according to a canonical redox control pathway. Little, however, is known about the redox control pathway used in early diverging metazoans. Our study examines the presence of known oxidative stress regulatory elements within non-bilaterian metazoans including free living and parasitic cnidarians, ctenophores, placozoans, and sponges. Cnidarians, with their pivotal position as the sister phylum to bilaterians, play an important role in understanding the evolutionary history of response to oxidative stress. Through comparative genomic and transcriptomic analysis our results show that Nrf homologs evolved early in metazoans, whereas Keap1 appeared later in the last common ancestor of cnidarians and bilaterians. However, key Nrf–Keap1 interacting domains are not conserved within the cnidarian lineage, suggesting this important pathway evolved with the radiation of bilaterians. Several known downstream Nrf targets are presentmore »
Functional annotations of three domestic animal genomes provide vital resources for comparative and agricultural research
Abstract Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticated animals. Here we present an expansive collection of datasets from eight diverse tissues in three important agricultural species: chicken ( Gallus gallus ), pig ( Sus scrofa ), and cattle ( Bos taurus ). Comparative analysis of these datasets and those from the human and mouse Encyclopedia of DNA Elements projects reveal that a core set of regulatory elements are functionally conserved independent of divergence between species, and that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes are also conserved. These datasets represent a unique opportunity for the emerging field of comparative epigenomics, as well as the agricultural research community, including species that are globally important food resources.
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- Nature Communications
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- National Science Foundation
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