科學家長期以來一直認為在學習和記憶過程中，特定的一些基因必定被激發(fā),，以改變大腦內部神經(jīng)的活動,。這些基因表達的中斷會導致癲癇等異常癥狀。但是確認所有這些基因是一項很困難的工作,。在《BMC Neuroscience》上,，來自Carnegie Mellon大學的科學家顯示了用一種全新的計算方法能快速確定這些基因,。
來自神經(jīng)基礎認知中心的生物科學助理教授Alison Barth說：“這項成果將最終得到治療神經(jīng)疾病的新藥物。同時我們也希望我們的工作能為研究者在分子水平上了解學習和記憶形成過程中神經(jīng)的改變帶來幫助,。”
在動物學習和記憶過程中,，大腦中特殊的神經(jīng)元會被激活。這些分子變化導致神經(jīng)元功能改變,。神經(jīng)科學家一直知道有兩種因子——CREB和zif268起到激活基因的作用,。CREB和zif268是轉錄因子。
Carnegie Mellon的小組創(chuàng)造了一種一步步尋找被CREB和zif268激活的基因的計算機方法,。他們找到了大約20000個相關基因,。計算機程序在人類和老鼠基因組中發(fā)現(xiàn)了數(shù)百個和CREB或者zif268結合的基因。而其中絕大部分之前從未被確認為CREB和zif268的目標過,。
Schwartz認為：“這意味著這些基因和學習及記憶相關,。在不同物種中起到類似作用的基因被認為有著很重要的作用，因為他們在進化過程中得到保留,。”小組將他們的結果在網(wǎng)上公布,，現(xiàn)在他們的在線數(shù)據(jù)庫中包含了基因名稱、符號和編號等信息——這些信息通常是不會被全部收集的,。
原文鏈接：http://www.physorg.com/news96118776.html
譯自：physorg.com
原始出處:
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.
