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The Six proteins (sine oculis) are a family of homeodomain transcription factors that share a conserved DNA binding domain. Six2, Six4 (AREC3) and Six5 bind to the same DNA sequence, indicating that they may regulate the same target genes. Six1 and Six4 are both capable of transactivating MEF3 site containing reporter genes, such as myogenin. It has been demonstrated that alterations to homeobox-containing genes may result in cancer. Six1 expression has been shown to be absent or low in normal adult tissues, although it is expressed in several tumor types, including breast carcinoma. Six1 overexpression has been shown to abrogate the G2 cell cycle checkpoint. Six2 is highly expressed in fetal tissues but expression is limited in adult tissues.