The 5′ domain of HOTAIR could bind polycomb repressive complex 2 (PRC2) and leads to a histone H3 lysine27 trimethylation (H3K27me3) in the HOXD locus, while the 3′ domain connects to the LSD1/CoREST/REST complex with H3 lysine 4 demethylation, together regulating the various downstream genes and promoting cancer cell metastasis [42]. The gene discussed is REST; the disease is cancer.