The RE1-Silencing Transcription factor (REST) is essential for neuronal differentiation. Here, we report the first 18.5-angstrom electron microscopy structure of human REST. The refined electron map suggests that REST forms a torus that can accommodate DNA double-helix in the central hole. Additionally, we quantitatively described REST binding to the canonical DNA sequence of the neuron-restrictive silencer element. We developed protocols for the expression and purification of full-length REST and the shortened variant REST-N62 produced by alternative splicing. We tested the mutual interaction of full-length REST and the splicing variant REST-N62. Revealed structure-function relationships of master neuronal repressor REST will allow finding new biological ways of prevention and treatment of neurodegenerative disorders and diseases.

CEITEC Masaryk University Brno Czech Republic

Institute of Biophysics of the Czech Academy of Sciences Scientific Incubator Královopolská 135 Brno 612 65 Czech Republic

LifeB FGP NCBR Faculty of Science Masaryk University Kamenice 753 5 Brno 625 00 Czech Republic

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