Kang C J, Sheridan C, Koshland M E
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Immunity. 1998 Mar;8(3):285-95. doi: 10.1016/s1074-7613(00)80534-8.
Interleukin-2 (IL-2)-induced transcription of the J chain gene was used as a model for analyzing cytokine regulation during B cell development. To determine whether IL-2 signals are targeted to a J chain gene enhancer as well as to its promoter, the sequences flanking the J chain gene were first examined for DNase I hypersensitivity. Of six sites identified, two strong ones, 7.5 kb upstream of the J chain gene, were found to be associated with an enhancer that is active only during the antigen-driven stages of B cell development. Further analyses of the enhancer in the IL-2-responsive presecretor BCL1 cells showed that the enhancer is activated at this stage by an IL-2 signal that functions by opening the enhancer chromatin and stimulating STAT5 to bind to a STAT5 element critical for the enhancer induction. Moreover, after this early induction stage, the enhancer was shown to be constitutively open and active in terminally differentiated plasma cells.
白细胞介素-2（IL-2）诱导的J链基因转录被用作分析B细胞发育过程中细胞因子调控的模型。为了确定IL-2信号是否靶向J链基因增强子及其启动子，首先检查了J链基因侧翼序列的DNase I超敏性。在鉴定出的六个位点中，发现两个强位点位于J链基因上游7.5 kb处，与一个仅在B细胞发育的抗原驱动阶段活跃的增强子相关。对IL-2反应性前分泌型BCL1细胞中增强子的进一步分析表明，该增强子在此阶段被IL-2信号激活，该信号通过打开增强子染色质并刺激STAT5结合到对增强子诱导至关重要 的STAT5元件上发挥作用。此外，在这个早期诱导阶段之后，该增强子在终末分化的浆细胞中显示为组成性开放且活跃。
