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学術論文

Active DNA demethylation of developmental cis-regulatory regions predates vertebrate origins

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Voronov,  Danila       
Max Planck Research Group Biological Clocks (Kaiser), Max Planck Institute for Evolutionary Biology, Max Planck Society;

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フルテキスト (公開)

sciadv.abn2258.pdf
(出版社版), 6MB

付随資料 (公開)

sciadv.abn2258_sm.pdf
(付録資料), 42MB

sciadv.abn2258_tables_s1_to_s13.zip
(付録資料), 969KB

引用

Skvortsova, K., Bertrand, S., Voronov, D., Duckett, P. E., Ross, S. E., Magri, M. S., Maeso, I., Weatheritt, R. J., Gómez Skarmeta, J. L., Arnone, M. I., Escriva, H., & Bogdanovic, O. (2022). Active DNA demethylation of developmental cis-regulatory regions predates vertebrate origins. Science Advances, 8(48):. doi:10.1126/sciadv.abn2258.


引用: https://hdl.handle.net/21.11116/0000-000C-DCF3-A
要旨
DNA methylation [5-methylcytosine (5mC)] is a repressive gene-regulatory mark required for vertebrate embryogenesis. Genomic 5mC is tightly regulated through the action of DNA methyltransferases, which deposit 5mC, and ten-eleven translocation (TET) enzymes, which participate in its active removal through the formation of 5-hydroxymethylcytosine (5hmC). TET enzymes are essential for mammalian gastrulation and activation of vertebrate developmental enhancers; however, to date, a clear picture of 5hmC function, abundance, and genomic distribution in nonvertebrate lineages is lacking. By using base-resolution 5mC and 5hmC quantification during sea urchin and lancelet embryogenesis, we shed light on the roles of nonvertebrate 5hmC and TET enzymes. We find that these invertebrate deuterostomes use TET enzymes for targeted demethylation of regulatory regions associated with developmental genes and show that the complement of identified 5hmC-regulated genes is conserved to vertebrates. This work demonstrates that active 5mC removal from regulatory regions is a common feature of deuterostome embryogenesis suggestive of an unexpected deep conservation of a major gene-regulatory module.