YY1 negatively regulates mouse myelin proteolipid protein (Plp1) gene expression in oligodendroglial cells.
YY1 negatively regulates mouse myelin proteolipid protein (Plp1) gene expression in oligodendroglial cells.
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YY1 负向调节少突胶质细胞中的小鼠髓磷脂蛋白脂质蛋白 (Plp1) 基因表达。
DOI：
10.1042/an20110021
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发表时间：
2011
期刊：
影响因子：
4.7
通讯作者：
Wight,PatriciaA
中科院分区：
文献类型：
--
作者：
Zolova,OlgaE;Wight,PatriciaA
YY1 （Yin and Yang 1）是一种多功能、普遍表达的锌指蛋白，可作为转录激活因子、抑制因子或启动元件结合蛋白。先前的研究表明，YY1调节髓磷脂PLP（蛋白脂蛋白）（PLP1/ PLP1）启动子驱动的报告基因的活性。然而，众所周知，plp1内含子1 DNA含有基因活性急剧增加所需的调控元件，与中枢神经系统发育的活跃髓鞘形成期一致。小鼠中的内含子包含多个YY1预期靶位点，其中一个位于正调控模块ASE （anti-silencer/enhancer）元件中。本研究的结果表明，YY1对未成熟少突胶质细胞系（Oli-neu）中aPlp1-lacZfusion基因[PLP(+)Z]的活性有负面影响，这是通过plp1内含子1 DNA中存在的序列介导的。然而，YY1并没有与ASE中所谓的位点结合（尽管该蛋白能够识别启动子中的目标位点），这表明YY1在Oli-neu细胞中下调PLP(+)Z活性并不是通过YY1与ASE序列的直接相互作用而发生的。先前对YY1条件敲除小鼠的研究表明，YY1对少突胶质细胞祖细胞的分化至关重要。然而，目前的研究表明YY1在未成熟少突胶质细胞中作为plp1基因表达的抑制因子（而不是激活因子）发挥作用。也许YY1的功能是在成熟的髓鞘少突胶质细胞需要大量蛋白质之前，在未成熟细胞中控制PLP的水平。
YY1 (Yin and Yang 1) is a multifunctional, ubiquitously expressed, zinc finger protein that can act as a transcriptional activator, repressor, or initiator element binding protein. Previous studies have shown that YY1 modulates the activity of reporter genes driven by the myelin PLP (proteolipid protein) (PLP1/Plp1) promoter. However, it is known thatPlp1intron 1 DNA contains regulatory elements that are required for the dramatic increase in gene activity, coincident with the active myelination period of CNS (central nervous system) development. The intron in mouse contains multiple prospective YY1 target sites including one within a positive regulatory module called the ASE (anti-silencer/enhancer) element. Results presented here demonstrate that YY1 has a negative effect on the activity of aPlp1-lacZfusion gene [PLP(+)Z] in an immature oligodendroglial cell line (Oli-neu) that is mediated through sequences present inPlp1intron 1 DNA. Yet YY1 does not bind to its alleged site in the ASE (even though the protein is capable of recognizing a target site in the promoter), indicating that the down-regulation of PLP(+)Z activity by YY1 in Oli-neu cells does not occur through a direct interaction of YY1 with the ASE sequence. Previous studies withYy1conditional knockout mice have demonstrated that YY1 is essential for the differentiation of oligodendrocyte progenitors. Nevertheless, the current study suggests that YY1 functions as a repressor (not an activator) ofPlp1gene expression in immature oligodendrocytes. Perhaps YY1 functions to keep the levels of PLP in check in immature cells before vast quantities of the protein are needed in mature myelinating oligodendrocytes.