Gene silencing quantitatively controls the function of a developmental trans-activator
Gene silencing quantitatively controls the function of a developmental trans-activator
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DOI：
10.1016/s1097-2765(02)00564-6
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发表时间：
2002-07-01
期刊：
影响因子：
16
通讯作者：
Reiner, SL
中科院分区：
文献类型：
--
作者：
Hutchins, AS;Mullen, AC;Reiner, SL
单个细胞如何产生具有不同命运的后代仍然知之甚少。我们研究了缺乏甲基CpG结合域蛋白2（MBD 2）的细胞，MBD 2是一种被认为将DNA甲基化与沉默染色质联系起来的分子。来自Mbd 2（-/-）小鼠的辅助T细胞表现出无序分化。IL-4是一组有限子代的特征，在Mbd 2（-/-）亲本和子代细胞中异位表达。MBD 2介导的沉默的丧失使得通常必需的激活剂加塔-3对IL-4诱导无效。加塔-3和MBD 2竞争作用，其中每个因子独立地和定量地调节是否建立可遗传的IL-4表达的二元选择。加塔-3的功能部分是从甲基化DNA中置换MBD 2。这些结果表明，激活和沉默信号整合，以提供空间和时间限制模式的基因活性。
How a single cell gives rise to progeny with differing fates remains poorly understood. We examined cells lacking methyl CpG binding domain protein-2 (MBD2), a molecule that has been proposed to link DNA methylation to silent chromatin. Helper T cells from Mbd2(-/-) mice exhibit disordered differentiation. IL-4, the signature of a restricted set of progeny, is expressed ectopically in Mbd2(-/-) parent and daughter cells. Loss of MBD2-mediated silencing renders the normally essential activator, Gata-3, dispensable for IL-4 induction. Gata-3 and MBD2 act in competition, wherein each factor independently, and quantitatively, regulates the binary choice of whether heritable IL-4 expression is established. Gata-3 functions, in part, to displace MBD2 from methylated DNA. These results suggest that activating and silencing signals integrate to provide spatially and temporally restricted patterns of gene activity.