科学家长期以来一直认为在学习和记忆过程中,特定的一些基因必定被激发,以改变大脑内部神经的活动。这些基因表达的中断会导致癫痫等异常症状。但是确认所有这些基因是一项很困难的工作。在《BMC Neuroscience》上,来自Carnegie Mellon大学的科学家显示了用一种全新的计算方法能快速确定这些基因。
来自神经基础认知中心的生物科学助理教授Alison Barth说:“这项成果将最终得到治疗神经疾病的新药物。同时我们也希望我们的工作能为研究者在分子水平上了解学习和记忆形成过程中神经的改变带来帮助。”
在动物学习和记忆过程中,大脑中特殊的神经元会被激活。这些分子变化导致神经元功能改变。神经科学家一直知道有两种因子——CREB和zif268起到激活基因的作用。CREB和zif268是转录因子。
Carnegie Mellon的小组创造了一种一步步寻找被CREB和zif268激活的基因的计算机方法。他们找到了大约20000个相关基因。计算机程序在人类和老鼠基因组中发现了数百个和CREB或者zif268结合的基因。而其中绝大部分之前从未被确认为CREB和zif268的目标过。
Schwartz认为:“这意味着这些基因和学习及记忆相关。在不同物种中起到类似作用的基因被认为有着很重要的作用,因为他们在进化过程中得到保留。”小组将他们的结果在网上公布,现在他们的在线数据库中包含了基因名称、符号和编号等信息——这些信息通常是不会被全部收集的。
原文链接:http://www.physorg.com/news96118776.html
译自:physorg.com
原始出处:
A comparative genomics approach to identifying the plasticity transcriptome
Andreas R Pfenning1 , Russell Schwartz1 ,2 and Alison L Barth2 , 3
1Department of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA
2Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA
3Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA 15213, USA
BMC Neuroscience 2007, 8:20 doi:10.1186/1471-2202-8-20
Abstract
Background
Neuronal activity regulates gene expression to control learning and memory, homeostasis of neuronal function, and pathological disease states such as epilepsy. A great deal of experimental evidence supports the involvement of two particular transcription factors in shaping the genomic response to neuronal activity and mediating plasticity: CREB and zif268 (egr-1, krox24, NGFI-A). The gene targets of these two transcription factors are of considerable interest, since they may help develop hypotheses about how neural activity is coupled to changes in neural function.
Results
We have developed a computational approach for identifying binding sites for these transcription factors within the promoter regions of annotated genes in the mouse, rat, and human genomes. By combining a robust search algorithm to identify discrete binding sites, a comparison of targets across species, and an analysis of binding site locations within promoter regions, we have defined a group of candidate genes that are strong CREB- or zif268 targets and are thus regulated by neural activity. Our analysis revealed that CREB and zif268 share a disproportionate number of targets in common and that these common targets are dominated by transcription factors.
Conclusion
These observations may enable a more detailed understanding of the regulatory networks that are induced by neural activity and contribute to the plasticity transcriptome. The target genes identified in this study will be a valuable resource for investigators who hope to define the functions of specific genes that underlie activity-dependent changes in neuronal properties.