Analysis of mouse teeth hyperplasia and gut tissue enlargement by mutation of transcription factor Bcl11b

Bcl11b/ Bcl11b是一种C_2H_2锌指转录因子，作为单倍体不足的肿瘤抑制因子。人类同源基因BCL11B的突变和缺失已经在人类t细胞急性淋巴细胞白血病（T-ALL）和小鼠胸腺淋巴瘤模型中被发现。我们研究了BCL11B是否直接影响p53信号通路，包括HDM2，一种用于p53降解的泛素连接酶。这是因为p^53通路调节细胞增殖和对DNA损伤的反应，以维持基因组的完整性。我们通过ChIP（染色质免疫沉淀）实验获得了BCL11B与人HDM2- p2启动子结合的结果，并以p^53依赖的方式抑制HDM2的表达。这些数据表明BCL11B影响p53-HDM2反馈回路的活性。这可能是Bcl11b S826G/KO小鼠T-ALL白血病转化、门牙发育障碍和肠隐窝扩大的机制。

Bcl11b/BCL11B is a C_2H_2 zinc finger transcription factor that acts as a haploinsufficient tumor suppressor. Mutations and deletion in the human orthologue BCL11B have been identified in human T-cell acute lymphoblastic leukemia (T-ALL) and a mouse model of thymic lymphomas. We have examined whether or not BCL11B directly affects the p^53 signaling pathway including HDM2, an ubiquitin ligase for p^53 degradation. This is because that the p^53 pathway regulates cell proliferation and the response to DNA damages to maintain genome integrity. We have obtained the results that BCL11B binds to human HDM2-P2 promoter by ChIP (chromatin immuno-precipitation) assay and inhibits HDM2 expression in a p^53-dependent manner. These date suggest that BCL11B affects the activity of the p53-HDM2 feedback loop. This may be a mechanism for the leukemic transformation in T-ALL and for the impairment of incisor development and the enlargement of intestine crypts in Bcl11b S826G/KO mouse.