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Title: | Evolution of a histone variant involved in compartmental regulation of NAD metabolism |
Author: | Guberovic, Iva Hurtado-Bagès, Sarah, 1990- Rivera Casas, Ciro Knobloch, Gunnar Malinverni, Roberto Valero, Vanesa Leger, Michelle M. Garcia, Jesús Basquin, Jerome Gómez de Cedron, Marta Frigolé Vivas, Marta Cheema, Manjinder S. Pérez, Ainhoa Ausió, Juan Ramírez de Molina, Ana Salvatella i Giralt, Xavier Ruiz Trillo, Iñaki Eirin Lopez, Jose M. Ladurner, Andreas G. Buschbeck, Marcus |
Keywords: | Cromatina Metabolisme Histones Chromatin Metabolism Histones |
Issue Date: | 9-Dec-2021 |
Abstract: | NAD metabolism is essential for all forms of life. Compartmental regulation of NAD(+) consumption, especially between the nucleus and the mitochondria, is required for energy homeostasis. However, how compartmental regulation evolved remains unclear. In the present study, we investigated the evolution of the macrodomain-containing histone variant macroH2A1.1, an integral chromatin component that limits nuclear NAD(+) consumption by inhibiting poly(ADP-ribose) polymerase 1 in vertebrate cells. We found that macroH2A originated in premetazoan protists. The crystal structure of the macroH2A macrodomain from the protist Capsaspora owczarzaki allowed us to identify highly conserved principles of ligand binding and pinpoint key residue substitutions, selected for during the evolution of the vertebrate stem lineage. Metabolic characterization of the Capsaspora lifecycle suggested that the metabolic function of macroH2A was associated with nonproliferative stages. Taken together, we provide insight into the evolution of a chromatin element involved in compartmental NAD regulation, relevant for understanding its metabolism and potential therapeutic applications. MacroH2A histone variants originated before the split of fungi and animals. ADP-ribose binding is an ancestral feature of their macrodomains and is linked to the compartmental regulation of NAD metabolism. This function was selected for during the evolution of metazoans. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1038/s41594-021-00692-5 |
It is part of: | Nature Structural & Molecular Biology, 2021, vol. 28, num. 12, p. 1009-1019 |
URI: | http://hdl.handle.net/2445/183063 |
Related resource: | https://doi.org/10.1038/s41594-021-00692-5 |
ISSN: | 1545-9985 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) Publicacions de projectes de recerca finançats per la UE |
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Guberovic_et_al_NSMB2021.pdf | 1.06 MB | Adobe PDF | View/Open |
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