Immunobiology and Cancer Research, Oklahoma Medical Research Foundation , Oklahoma City, OK , USA.
Department of Cell Biology, University of Oklahoma Health Sciences Center , Oklahoma City, OK , USA.
Front Immunol. 2014 Mar 19;5:113. doi: 10.3389/fimmu.2014.00113. eCollection 2014.
ARID3a/Bright is a DNA-binding protein that was originally discovered for its ability to increase immunoglobulin transcription in antigen-activated B cells. It interacts with DNA as a dimer through its ARID, or A/T-rich interacting domain. In association with other proteins, ARID3a increased transcription of the immunoglobulin heavy chain and led to improved chromatin accessibility of the heavy chain enhancer. Constitutive expression of ARID3a in B lineage cells resulted in autoantibody production, suggesting its regulation is important. Abnormal ARID3a expression has also been associated with increased proliferative capacity and malignancy. Roles for ARID3a in addition to interactions with the immunoglobulin locus were suggested by transgenic and knockout mouse models. Over-expression of ARID3a resulted in skewing of mature B cell subsets and altered gene expression patterns of follicular B cells, whereas loss of function resulted in loss of B1 lineage B cells and defects in hematopoiesis. More recent studies showed that loss of ARID3a in adult somatic cells promoted developmental plasticity, alterations in gene expression patterns, and lineage fate decisions. Together, these data suggest new regulatory roles for ARID3a. The genes influenced by ARID3a are likely to play pivotal roles in lineage decisions, highlighting the importance of this understudied transcription factor.
ARID3a/Bright 是一种 DNA 结合蛋白,最初因其能够增加抗原激活 B 细胞中的免疫球蛋白转录而被发现。它通过其 ARID(富含 A/T 的相互作用结构域)作为二聚体与 DNA 相互作用。与其他蛋白结合,ARID3a 增加了免疫球蛋白重链的转录,并导致重链增强子的染色质可及性提高。B 细胞谱系细胞中 ARID3a 的组成性表达导致自身抗体的产生,表明其调节作用很重要。异常的 ARID3a 表达也与增殖能力增加和恶性肿瘤有关。转基因和敲除小鼠模型提示 ARID3a 的作用除了与免疫球蛋白基因座相互作用之外。ARID3a 的过表达导致成熟 B 细胞亚群的倾斜和滤泡 B 细胞的基因表达模式改变,而功能丧失导致 B1 谱系 B 细胞的丧失和造血缺陷。最近的研究表明,成年体细胞中 ARID3a 的缺失促进了发育可塑性、基因表达模式的改变和谱系命运的决定。总之,这些数据表明 ARID3a 具有新的调节作用。受 ARID3a 影响的基因可能在谱系决定中发挥关键作用,突出了这个研究不足的转录因子的重要性。