Although the epigenetic silencing of p21 (possible to be reversed by HDIs) seems to be the main mechanism by which the p21 gene is down-regulated in tumours, the gene promoter activity can be additionally regulated and controlled by various transcriptional activators, such as p53, Sp1/Sp3, E-boxes, STAT proteins, or repressors, e.g., c-Myc or FBI-1, having their response elements located in distal or proximal promoter region of p21 [19,20,21,22,23]. The gene discussed is CDKN1A; the disease is neoplasm.