Evolution of a histone variant involved in compartmental regulation of NAD metabolism

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.

Bibliographic Details

Main Authors:	Guberovic, Iva, Hurtado-Bagès, Sarah, Rivera-Casas, Ciro, Knobloch, Gunnar, Malinverni, Roberto, Valero, Vanesa, Leger, Michelle M., García, Jesús, Basquin, Jerome, Gómez de Cedrón, Marta, Frigolé-Vivas, Marta, Cheema, Manjinder S., Pérez, Ainhoa, Ausió, Juan, Ramírez de Molina, Ana, Salvatella, Xavier, Ruiz-Trillo, Iñaki, Eirín-López, José María, Ladurner, Andreas G., Buschbeck, Marcus
Other Authors:	Max Planck Society
Format:	artículo biblioteca
Published:	Nature Publishing Group 2021-12-09
Subjects:	Histone variants, Metabolism, X-ray crystallography,
Online Access:	http://hdl.handle.net/10261/263537 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100005774 http://dx.doi.org/10.13039/501100004189 http://dx.doi.org/10.13039/501100002809 http://dx.doi.org/10.13039/100012818
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