Project description:Adaptive immunity and the five vertebrate NF-kB/Rel family members first appeared in cartilaginous fish, suggesting that NF-kB family expansion allowed the acquisition of new functions to regulate adaptive immune responses. Transcriptome profiling revealed that, even in macrophages, the NF-kB family member, c-Rel, most potently regulates a cytokine gene linked to adaptive immunity, Il12b, with limiting roles at key regulators of innate immunity. Neofunctionalization of c-Rel to regulate Il12b depends on its unique DNA-binding properties, which we examined using structural, biochemical, functional, and genomic approaches. Among our findings was functional c-Rel homodimer binding to motifs with little resemblance to canonical NF-kB motifs. To determine whether c-Rel’s unique binding properties drove c-Rel-RelA divergence, we compared binding properties in various vertebrate species. c-Rel-RelA binding properties diverged in mammals and amphibians but were comparable in earlier vertebrates, suggesting that divergent DNA binding emerged relatively late during vertebrate evolution to support increasing complexity of adaptive immune regulation.
Project description:Adaptive immunity and the five vertebrate NF-kB/Rel family members first appeared in cartilaginous fish, suggesting that NF-kB family expansion allowed the acquisition of new functions to regulate adaptive immune responses. Transcriptome profiling revealed that, even in macrophages, the NF-kB family member, c-Rel, most potently regulates a cytokine gene linked to adaptive immunity, Il12b, with limiting roles at key regulators of innate immunity. Neofunctionalization of c-Rel to regulate Il12b depends on its unique DNA-binding properties, which we examined using structural, biochemical, functional, and genomic approaches. Among our findings was functional c-Rel homodimer binding to motifs with little resemblance to canonical NF-kB motifs. To determine whether c-Rel’s unique binding properties drove c-Rel-RelA divergence, we compared binding properties in various vertebrate species. c-Rel-RelA binding properties diverged in mammals and amphibians but were comparable in earlier vertebrates, suggesting that divergent DNA binding emerged relatively late during vertebrate evolution to support increasing complexity of adaptive immune regulation.
Project description:The brain requires complex mechanisms of genome regulation to encode and store behavioural information. In mammals, DNA methylation deposited at non-CG dinucleotides characterises brain epigenomes. However, it is unclear to what extent this non-canonical form of DNA methylation is evolutionarily conserved. To test this we profile brain cytosine methylation across the major vertebrate lineages, amphioxus, honeybee and octopus, finding that non-CG methylation in adult brain methylomes is restricted to vertebrates. In vertebrates, the genomic patterns of non-CG do not recapitulate those of CG methylation, yet both patterns are deeply conserved. Whereas low levels of gene body CG methylation demarcate a set of developmental transcription factors across tissues and species, a distinct set of neurodevelopmental genes accumulate non-CG methylation in neural tissues. We further show that the establishment of this methylation context coincides with the origin of the “writer” of non-CG methylation, the methyltransferase DNMT3A, and the “reader”, the methyl-CpG binding protein 2 (MeCP2), fuelled by the ancestral whole genome duplication in vertebrates. Surprisingly, MeCP2 evolved in a stepwise process, from an ancestral MBD4 protein with a dual role in transcriptional regulation and DNA repair in chordates. In sum, we show how a novel neural epigenomic layer assembled at the root of vertebrates and gained new regulatory roles partly independent from CG methylation, which could have fostered the sophisticated cognitive repertoires found in the vertebrate lineage.
Project description:We investigated the role of basal ppGpp levels in Synechococcus elongatus PCC7942 in adaptation to darkness. We performed RNA-seq experiments using the rel- relA+ and the rel- relAE335Q strain at dusk and during exposure to 12 h of darkness. We show that basal ppGpp levels is not sufficient for restoration of appropriate transcriptional shutdown in response to darkness.
Project description:We investigated the role of the basal levels of ppGpp in Synechococcus elongatus PCC7942 in constant light. We performed RNA-seq experiments using the rel- + relA+ and rel- + relAE335Q strains and show that basal levels of ppGpp are required for regulation of global transcription in light.