Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes
Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes
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DOI：
10.1073/pnas.0401827101
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发表时间：
2004-07-13
影响因子：
11.1
通讯作者：
Buckley, NJ
中科院分区：
文献类型：
--
作者：
Bruce, AW;Donaldson, IJ;Buckley, NJ
全基因组测序计划的完成提供了生命的遗传指令。然而，虽然基因编码区的鉴定已经取得了进展，转录调控基序的定位却进展缓慢。为了理解如何建立和维持不同的表达谱，需要更好地理解这些序列及其反式作用因子。在此，我们已经使用了一个结合在硅片和生物化学的方法来确定结合位点[阻遏元件1 /神经元限制性沉默元件（RE 1/NRSE）]和潜在的靶基因RE 1沉默转录因子/神经元限制性沉默因子（REST/NRSF）在人类，小鼠和红鳍东方基因组。我们已经使用这种全基因组分析，以确定1,892人，1,894小鼠和554河豚IRE 1/NRSE，并在可搜索的数据库中呈现其位置和基因连锁。此外，我们确定了一个体内层次结构，其中RE 1/NRSE的不同子集与REST/NRSF的高水平相互作用，而其他人只在REST/NRSF水平升高的情况下作为真正的转录控制元件发挥作用。这些数据表明，个别RE 1/NRSE网站与REST/NRSF在一个特定的细胞类型的差异相互作用。这种结合生物信息学和生物化学的方法用于说明转录因子与其潜在结合位点相互作用并调节靶基因的选择性方式。此外，这种方法提供了一个独特的全基因组图谱的一个给定的转录因子结合位点，涉及建立特定的模式的神经元基因表达。
The completion of whole genome sequencing projects has provided the genetic instructions of life. However, whereas the identification of gene coding regions has progressed, the mapping of transcriptional regulatory motifs has moved more slowly. To understand how distinct expression profiles can be established and maintained, a greater understanding of these sequences and their trans-acting factors is required. Herein we have used a combined in silico and biochemical approach to identify binding sites [repressor element 1 / neuron-restrictive silencer element (RE1/NRSE)] and potential target genes of RE1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the human, mouse, and Fugu rubripes genomes. We have used this genomewide analysis to identify 1,892 human, 1,894 mouse, and 554 Fugu IRE1/NRSEs and present their location and gene linkages in a searchable database. Furthermore, we identified an in vivo hierarchy in which distinct subsets of RE1/NRSEs interact with enclogenous levels of REST/NRSF, whereas others function as bona fide transcriptional control elements only in the presence of elevated levels of REST/NRSF. These data show that individual RE1/NRSE sites interact differentially with REST/NRSF within a particular cell type. This combined bioinformatic and biochemical approach serves to illustrate the selective manner in which a transcription factor interacts with its potential binding sites and regulates target genes. In addition, this approach provides a unique whole-genome map for a given transcription factor-binding site implicated in establishing specific patterns of neuronal gene expression.