BMI1 gene

The BMI1 gene (BMI1 stands for: B Lymphoma Mo-MLV Insertion Region 1 Homolog also for Proto-Oncogene, Polycomb Ring Finger) is a protein coding gene located on chromosome 10p12.2. An important paralog of this gene is PCGF2.

The BMI1 gene is an oncogene. The gene encodes a ring finger protein of the same name, which is a major component of the Polycomb Group Complex 1 (PRC1). Through chromatin remodeling, this complex functions as an essential epigenetic repressor of several regulatory genes involved in embryonic development and self-renewal and proliferation in somatic stem cells. The encoded BMI1 protein also plays a central role in DNA damage repair.

The encoded protein is a component of a multiprotein PRC1-like Polycomb group (PcG) complex, a class of complexes required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. The PcG-PRC1 complex acts by remodeling chromatin and modifying histones; it mediates monoubiquitination of histone H2A 'Lys-119', resulting in heritable changes in chromatin expressivity (Wang H et al. 2004; Gray F et al. 2016). The complex consisting of RNF2, UB2D3 and BMI1 binds nucleosomes and is only active with the nucleosomal histone H2A (McGinty RK et al. 2014). In the PRC1-like complex, it regulates the E3 ubiquitin-protein ligase activity of RNF2/RING2 (Wang H et al. 2004)

In cutaneous melanoma, BMI1 drives epithelial-mesenchymal transition programs and thus metastasis, while it has little effect on the proliferation or growth of the primary tumor (Wilson MM et al.2023). A melanocyte-specific deletion of BMI1 leads to premature hair graying and a gradual loss of cells of the melanocyte lineage in mice. Depilation exacerbates this hair graying defect and accelerates the loss of McSCs in early hair cycles, suggesting that BMI1 protects McSCs from stress. In addition, loss of BMI1 downregulated the glutathione S-transferase enzymes Gsta1 and Gsta2, which can suppress oxidative stress. Accordingly, treatment with the antioxidant N-acetylcysteine (NAC) partially restored melanocyte expansion (Wilson MM et al.2023).

Aberrant expression of the BMI gene is associated with numerous types of cancer and is linked to resistance to certain chemotherapies. Diseases associated with BMI1 include mantle cell lymphoma and leukemia.

1. McGinty RK et al. (2014) Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature 514:591-596.
2. Gray F et al. (2016) BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization. Nat Commun 7:13343.
3. Wang H et al. (2004) Role of histone H2A ubiquitination in Polycomb silencing. Nature 431:873-878.
4. Wilson MM et al.(2023) BMI1 is required for melanocyte stem cell maintenance and hair pigmentation. Pigment Cell Melanoma Res 36:399-406.