Proposed mechanism of HOTAIR mediated gene silencing of 40 kb of the HOXD locus, which is involved in developmental patterning. The HOTAIR lncRNA is transcribed from the HOXC locus and functions in the binding and recruitment and binding of the PRC2 and LSD1 complex to the HOXD locus. For clarity, only the PRC2 complex is indicated in the above figure. Through an undetermined mechanism, the HOTAIR-PRC2-LSD1 complex is redirected to the HOXD locus on chromosome 2 where genes involved in metastasis suppression are silenced through H3K27 methylation and H3K4 demethylation. This drives breast cancer cells to develop gene expression patterns that more closely resemble embryonic fibroblasts than epithelial cells.