Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection.
Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection.
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DOI：
10.1016/j.neuron.2008.11.029
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发表时间：
2008-12-26
期刊：
影响因子：
16.2
通讯作者：
Greenberg, Michael E.
中科院分区：
文献类型：
--
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
尽管已知许多转录因子控制神经发育的重要方面，但由这些因子直接调控的全基因组程序尚不清楚。我们已经确定了由MEF2激活的遗传程序的特征，MEF2是活性依赖性突触发育的关键调节因子。这些MEF2靶基因在突触中具有不同的功能，揭示了MEF2在突触发育中的广泛作用。MEF2的几个目标是突变的人类神经系统疾病，包括癫痫和自闭症谱系障碍，这表明这些疾病可能是由控制突触发育的活性依赖性基因程序的中断引起的。我们的分析还表明，神经元活动促进了许多MEF2靶基因的多聚腺苷酸化位点的替代使用，导致产生截短的mRNA，这些mRNA可能具有与全长mRNA不同的功能。总之，这些分析表明，普遍表达的转录因子MEF2调节神经元中控制突触发育的复杂转录程序。
Although many transcription factors are known to control important aspects of neural development, the genome-wide programs that are directly regulated by these factors are not known. We have characterized the genetic program that is activated by MEF2, a key regulator of activity-dependent synapse development. These MEF2 target genes have diverse functions at synapses, revealing a broad role for MEF2 in synapse development. Several of the MEF2 targets are mutated in human neurological disorders including epilepsy and autism-spectrum disorders, suggesting that these disorders may be caused by disruption of an activity-dependent gene program that controls synapse development. Our analyses also reveal that neuronal activity promotes alternative polyadenylation site usage at many of the MEF2 target genes, leading to the production of truncated mRNAs that may have different functions than their full-length counterparts. Taken together, these analyses suggest that the ubiquitously expressed transcription factor MEF2 regulates an intricate transcriptional program in neurons that controls synapse development.
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