The characterization of macroH2A beyond vertebrates supports an ancestral origin and conserved role for histone variants in chromatin

ABSTRACT

Histone variants play a critical role in chromatin structure and epigenetic regulation. These “deviant” proteins have been historically considered as the evolutionary descendants of ancestral canonical histones, helping specialize the nucleosome structure during eukaryotic evolution. Such view is now challenged by 2 major observations: first, canonical histones present extremely unique features not shared with any other genes; second, histone variants are widespread across many eukaryotic groups. The present work further supports the ancestral nature of histone variants by providing the first in vivo characterization of a functional macroH2A histone (a variant long defined as a specific refinement of vertebrate chromatin) in a non-vertebrate organism (the mussel Mytilus) revealing its recruitment into heterochromatic fractions of actively proliferating tissues. Combined with in silico analyses of genomic data, these results provide evidence for the widespread presence of macroH2A in metazoan animals, as well as in the holozoan Capsaspora, supporting an evolutionary origin for this histone variant lineage before the radiation of Filozoans (including Filasterea, Choanoflagellata and Metazoa). Overall, the results presented in this work help configure a new evolutionary scenario in which histone variants, rather than modern “deviants” of canonical histones, would constitute ancient components of eukaryotic chromatin.

KEYWORDS:

• Chromatin
• epigenetics
• evolution
• function
• histone variants
• In Vivo
• metazoans
• nucleosome
• structure

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Shahid Karim at the Department of Biological Sciences of the University of Southern Mississippi for providing us with salivary glands from the tick Amblyomma maculatum, Nancy Sherwood from the Biology Department at the University of Victoria for providing us with several specimens of the lancelet Branchiostoma floridae, and Robert Burke from the Biochemistry and Microbiology Department at the University of Victoria for providing us with tissue samples of the sea urchin Strongylocentrotus purpuratus. We are grateful to Angel Vizoso-Vazquez, Esperanza Cerdan and Josefina Mendez at the Department of Cellular and Molecular Biology (University of A Coruna, Spain) for providing CR-C with lab space and support during macroH2A purification. We are also very thankful to Frederic Berger, Juan Pedro Martinez Camacho, Steven Henikoff and Paul Talbert, as well as to the colleagues attending the 2015 Gordon Conference on Epigenetics, for their comments and feedback on an earlier version of this manuscript. This is contribution #1 of the Marine Education and Research Center of the Institute for Water and the Environment at Florida International University.

Funding

This work was supported by grants from the Biomolecular Sciences Institute (800005997) and the College of Arts, Sciences and Education (CASE) at Florida International University (JME-L); and by a Natural Sciences and Engineering Research Council of Canada (NSERC) 46399-2012 grant to JA. CR-C was supported by an FPU fellowship from the Government of Spain.