Instituto de Neurociencias (Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas), Av. Santiago Ramón y Cajal s/n. Sant Joan d'Alacant, 03550, Alicante, Spain.
Mol Neurobiol. 2015;51(3):1071-88. doi: 10.1007/s12035-014-8772-z. Epub 2014 Jun 17.
Activity-driven transcription is a key event associated with long-lasting forms of neuronal plasticity. Despite the efforts to investigate the regulatory mechanisms that control this complex process and the important advances in the knowledge of the function of many activity-induced genes in neurons, as well as the specific contribution of activity-regulated transcription factors, our understanding of how activity-driven transcription operates at the systems biology level is still very limited. This review focuses on the research of neuronal activity-driven transcription from an "omics" perspective. We will discuss the different high-throughput approaches undertaken to characterize the gene programs downstream of specific activity-regulated transcription factors, including CREB, SRF, MeCP2, Fos, Npas4, and others, and the interplay between epigenetic and transcriptional mechanisms underlying neuronal plasticity changes. Although basic questions remain unanswered and important challenges still lie ahead, the refinement of genome-wide techniques for investigating the neuronal transcriptome and epigenome promises great advances.
活性驱动的转录是与神经元长时程可塑性相关的关键事件。尽管人们努力研究控制这一复杂过程的调节机制,并且在神经元中许多活性诱导基因的功能以及活性调节转录因子的特定贡献方面取得了重要进展,但我们对于活性驱动的转录在系统生物学水平上如何运作的理解仍然非常有限。本综述从“组学”的角度关注神经元活性驱动的转录。我们将讨论为了描述特定活性调节转录因子(包括 CREB、SRF、MeCP2、Fos、Npas4 等)下游的基因程序而进行的不同高通量方法,以及神经元可塑性变化背后的表观遗传和转录机制之间的相互作用。尽管基本问题仍未得到解答,而且仍然存在重要挑战,但用于研究神经元转录组和表观基因组的全基因组技术的完善有望取得重大进展。