NFIL3 and cAMP Response Element-Binding Protein Form a Transcriptional Feedforward Loop that Controls Neuronal Regeneration-Associated Gene Expression
NFIL3 and cAMP Response Element-Binding Protein Form a Transcriptional Feedforward Loop that Controls Neuronal Regeneration-Associated Gene Expression
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DOI：
10.1523/jneurosci.3938-09.2009
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发表时间：
2009-12-09
影响因子：
5.3
通讯作者：
van Kesteren, Ronald E.
中科院分区：
文献类型：
--
作者：
MacGillavry, Harold D.;Stam, Floor J.;van Kesteren, Ronald E.
受损神经元的成功再生依赖于神经元内在基因的协调表达。然而，目前还没有全面的看法，转录调控机制的神经元再生。我们使用高含量的细胞筛选来研究62个转录因子对再生神经元生长的功能贡献。鉴定出十种增加或减少神经突生长的转录因子。其中之一，NFIL3，在体内成功再生过程中特异性上调。然而，奇怪的是，NFIL3的敲低和显性负性NFIL3的过表达都增加了神经突的生长。我们的数据表明，NFIL3，与CREB一起，形成一个不连贯的前馈转录调控环，其中NFIL3作为CREB诱导的再生相关基因的负调控因子。
Successful regeneration of damaged neurons depends on the coordinated expression of neuron-intrinsic genes. At present however, there is no comprehensive view of the transcriptional regulatory mechanisms underlying neuronal regeneration. We used high-content cellular screening to investigate the functional contribution of 62 transcription factors to regenerative neuron outgrowth. Ten transcription factors are identified that either increase or decrease neurite outgrowth. One of these, NFIL3, is specifically upregulated during successful regeneration in vivo. Paradoxically however, knockdown of NFIL3 and overexpression of dominant-negative NFIL3 both increase neurite outgrowth. Our data show that NFIL3, together with CREB, forms an incoherent feedforward transcriptional regulatory loop in which NFIL3 acts as a negative regulator of CREB-induced regeneration-associated genes.