With its noncatalytic domains, DNA-binding regions, and a catalytic core targeting the histone tails, LSD1-CoREST (lysine-specific demethylase 1; REST corepressor) is an ideal model system to study the interplay between DNA binding and histone modification in nucleosome recognition. To this end, we covalently associated LSD1-CoREST to semisynthetic nucleosomal particles. This enabled biochemical and biophysical characterizations of nucleosome binding and structural elucidation by small-angle X-ray scattering, which was extensively validated through binding assays and site-directed mutagenesis of functional interfaces. Our results suggest that LSD1-CoREST functions as an ergonomic clamp that induces the detachment of the H3 histone tail from the nucleosomal DNA to make it available for capture by the enzyme active site. The key notion emerging from these studies is the inherently competitive nature of the binding interactions because nucleosome tails, chromatin modifiers, transcription factors, and DNA represent sites for multiple and often mutually exclusive interactions. Significance The correct and regulated readout of epigenetic marks on chromatin is essential to modulate gene expression in living cells. The regulation of chromatin accessibility is ensured by such epigenetic tags, which form a platform for the binding of specific enzymatic modules. A clear example of this mechanism is represented by the histone demethylase LSD1-CoREST, which removes methylation marks from lysine 4 of histone protein H3. We developed a crosslinking technology to capture this histone demethylase in contact with the nucleosome and used this methodology to explore the structural and biophysical properties of this complex. This is one of the very few successful attempts to visualize the molecular mechanism underlying the recognition of the nucleosomal substrate by a histone-modifying enzyme complex.