BMI1（B细胞特异性莫洛尼鼠白血病病毒整合位点1，B-cell-specific Moloney murine leukemia virus integration site 1）是一种重要的多梳基因家族（Polycomb group genes，PcG）成员，该家族在表观遗传调控中起关键作用，通过形成多梳抑制复合物（PRC1）参与染色质修饰，抑制靶基因表达以维持细胞身份和干细胞自我更新。BMI1的核心功能是沉默细胞分化相关基因（如INK4a/ARF位点的p16和p14），从而促进干细胞增殖并阻止衰老。其表达产物（BMI1蛋白）通过与其他PRC1组分（如RING1B）结合，催化组蛋白H2A的泛素化（H2AK119ub），导致染色质紧缩并抑制转录。BMI1的作用位点主要位于细胞核，尤其在胚胎干细胞、造血干细胞和神经干细胞中高表达。突变或缺失BMI1会导致干细胞耗竭、组织萎缩和早衰，例如BMI1敲除小鼠表现为造血障碍和神经系统退化。该基因与多种癌症密切相关，过表达时通过抑制抑癌基因（如p16）促进肿瘤发生，常见于神经母细胞瘤、乳腺癌和白血病；而低表达则可能触发细胞衰老或分化。BMI1还参与DNA损伤修复和氧化应激响应，其异常表达会影响其他表观遗传调控因子（如EZH2）的功能。多梳基因家族的共性是通过PRC1和PRC2复合物协同维持基因沉默状态，调控发育和细胞命运决定。若BMI1过表达，可能增强干细胞特性并导致肿瘤耐药性；反之，表达降低会诱发分化或衰老表型，某些情况下可被用于癌症治疗靶点。需要注意的是，中文术语"多梳基因"对应英文"Polycomb group genes"，而"表观遗传调控"指不改变DNA序列的基因表达调控机制。

BMI1, or B-cell-specific Moloney murine leukemia virus integration site 1, is a critical member of the Polycomb group (PcG) gene family that plays a pivotal role in epigenetic regulation by maintaining cell identity and stem cell self-renewal. As a core component of the Polycomb Repressive Complex 1 (PRC1), BMI1 functions within the nucleus to silence target genes involved in cell differentiation and senescence, most notably the INK4a/ARF locus which encodes the tumor suppressors p16 and p14. Mechanistically, BMI1 interacts with other PRC1 subunits, such as RING1B, to catalyze the monoubiquitination of histone H2A at lysine 119 (H2AK119ub), a modification that compacts chromatin structure and represses transcriptional activity without altering the underlying DNA sequence. This precise epigenetic silencing is essential for preventing premature differentiation and cellular aging, allowing stem cells in the hematopoietic, neural, and embryonic lineages to maintain their proliferative capacity; consequently, the loss or mutation of BMI1 leads to stem cell exhaustion, tissue atrophy, hematopoietic failure, and neurodegeneration, as evidenced by the phenotypes observed in knockout mouse models. In the context of human disease, BMI1 is frequently overexpressed in various malignancies, including neuroblastoma, breast cancer, and leukemia, where it promotes tumorigenesis by sustaining the undifferentiated state of cancer cells and conferring resistance to therapy, whereas its downregulation can trigger differentiation or senescence, making it a potential therapeutic target. Beyond its canonical role in chromatin remodeling, BMI1 also contributes to DNA damage repair and oxidative stress responses, and its dysregulation can disrupt the function of other epigenetic regulators such as EZH2, highlighting its central position in the coordinated network of PRC1 and PRC2 complexes that govern developmental trajectories and cell fate decisions.

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