BMI1 is a component of the polycomb-repres-sor complex 1 (PRC1), which plays important roles in gene silencing. Together with the polycomb-repressor complex 2 (PRC2), which trimethylates histone H3 at the K27 residue, it brings about robust chromatin silencing through ubiquitination of histone H2A at the K119 residue. The most well-characterized target of BMI1 is the Ink4a-Arf locus, which is suppressed through chromatin modification.2 Consistent with its role in the suppression of the Ink4a-Arf locus, BMI1 is also a strong regulator of senescence. Mouse embryonic fibroblasts lacking BMI1 expression undergo senescence by passage 3, resulting from high expression of p16lnk4a and p19Arf. BMI1 has been shown to be important for self-renewal of neuronal, intestinal and hematopoietic stem cells. BMI1 functions as an oncopro-tein and is over-expressed in cancers. Recent studies indicated roles of BMI1 overexpression in metastasis. It collaborates with Twisti to induce epithelial to mesenchymal transition (EMT) in head and neck cancer cells through downregulation of E-cadherin and p16lnk4a. The same study reported that BMI1 is also required for the expansion of the tumor-initiating cells.
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