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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genome-wide analysis of repressor element 1 silencing transcription factoreuron-restrictive silencing factor (REST/NRSF) target genes.
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Genome-wide analysis of repressor element 1 silencing transcription factoreuron-restrictive silencing factor (REST/NRSF) target genes.

机译：全基因组分析的阻遏因子1沉默转录因子/神经元限制性沉默因子（REST / NRSF）目标基因。

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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 1euron-restrictive silencer element (RE1/NRSE)] and potential target genes of RE1 silencing transcription factoreuron-restrictive silencing factor (REST/NRSF) within the human, mouse, and Fugu rubripes genomes. We have used this genome-wide analysis to identify 1,892 human, 1,894 mouse, and 554 Fugu RE1/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 endogenous 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.
机译：全基因组测序项目的完成提供了生命的遗传学指导。然而，尽管基因编码区的鉴定已经取得进展，但转录调控基序的定位却更加缓慢。为了了解如何建立和维持不同的表达谱，需要对这些序列及其反式作用因子有更多的了解。在本文中，我们使用了计算机和生化相结合的方法来鉴定结合位点[阻遏物元件1 /神经元限制性沉默子（RE1 / NRSE）]和RE1沉默转录因子/神经元限制性沉默因子（REST / NRSF）的潜在靶基因）在人类，小鼠和河豚鼠的基因组中。我们已经使用这种全基因组分析来识别1,892人，1,894小鼠和554府河豚鼠RE1 / NRSE，并在可搜索的数据库中显示它们的位置和基因联系。此外，我们确定了一个体内层次结构，其中RE1 / NRSE的不同子集与内源水平的REST / NRSF相互作用，而其他子集仅在存在较高水平的REST / NRSF的情况下充当真正的转录控制元件。这些数据表明，单个RE1 / NRSE站点在特定细胞类型内与REST / NRSF的相互作用不同。这种组合的生物信息学和生化方法可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。另外，该方法为涉及建立神经元基因表达的特定模式的给定转录因子结合位点提供了独特的全基因组图。

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