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利用果蝇全基因组保守序列数据库鉴定功能相关的顺式调控增强子。

Use of a Drosophila genome-wide conserved sequence database to identify functionally related cis-regulatory enhancers.

机构信息

Neural Cell-Fate Determinants Section, NINDS, NIH, Bethesda, Maryland 20892, USA.

出版信息

Dev Dyn. 2012 Jan;241(1):169-89. doi: 10.1002/dvdy.22728. Epub 2011 Aug 30.

DOI:10.1002/dvdy.22728
PMID:22174086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3243966/
Abstract

BACKGROUND

Phylogenetic footprinting has revealed that cis-regulatory enhancers consist of conserved DNA sequence clusters (CSCs). Currently, there is no systematic approach for enhancer discovery and analysis that takes full-advantage of the sequence information within enhancer CSCs.

RESULTS

We have generated a Drosophila genome-wide database of conserved DNA consisting of >100,000 CSCs derived from EvoPrints spanning over 90% of the genome. cis-Decoder database search and alignment algorithms enable the discovery of functionally related enhancers. The program first identifies conserved repeat elements within an input enhancer and then searches the database for CSCs that score highly against the input CSC. Scoring is based on shared repeats as well as uniquely shared matches, and includes measures of the balance of shared elements, a diagnostic that has proven to be useful in predicting cis-regulatory function. To demonstrate the utility of these tools, a temporally-restricted CNS neuroblast enhancer was used to identify other functionally related enhancers and analyze their structural organization.

CONCLUSIONS

cis-Decoder reveals that co-regulating enhancers consist of combinations of overlapping shared sequence elements, providing insights into the mode of integration of multiple regulating transcription factors. The database and accompanying algorithms should prove useful in the discovery and analysis of enhancers involved in any developmental process.

摘要

背景

系统发生足迹分析揭示顺式调控增强子由保守的 DNA 序列簇（CSC）组成。目前，还没有一种系统的方法可以充分利用增强子 CSC 中的序列信息来发现和分析增强子。

结果

我们生成了一个包含超过 10 万个 CSC 的果蝇全基因组保守 DNA 数据库，这些 CSC 源自跨越基因组 90%以上的 EvoPrints。cis-Decoder 数据库搜索和比对算法可用于发现功能相关的增强子。该程序首先识别输入增强子中的保守重复元件，然后在数据库中搜索与输入 CSC 高度匹配的 CSC。评分基于共享的重复序列以及独特共享的匹配序列，并包括共享元素平衡的度量标准，该标准已被证明在预测顺式调控功能方面非常有用。为了演示这些工具的实用性，使用一个时间限制的中枢神经系统神经母细胞增强子来识别其他功能相关的增强子，并分析它们的结构组织。

结论

cis-Decoder 揭示了共同调控的增强子由重叠共享序列元件的组合组成，这为理解多个调节转录因子的整合模式提供了线索。该数据库和相关算法应该有助于发现和分析参与任何发育过程的增强子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/07c1b426e690/dvdy0241-0169-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/6c42954c44c8/dvdy0241-0169-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/ee8d3f44a741/dvdy0241-0169-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/7690a3a9c80a/dvdy0241-0169-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/5a0a1eb7c30f/dvdy0241-0169-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/9bd4ce17cde0/dvdy0241-0169-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/e6f0d8f40c7f/dvdy0241-0169-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/a327627d881b/dvdy0241-0169-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/d2e197fa9c3e/dvdy0241-0169-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/07c1b426e690/dvdy0241-0169-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/6c42954c44c8/dvdy0241-0169-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/ee8d3f44a741/dvdy0241-0169-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/7690a3a9c80a/dvdy0241-0169-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/5a0a1eb7c30f/dvdy0241-0169-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/9bd4ce17cde0/dvdy0241-0169-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/e6f0d8f40c7f/dvdy0241-0169-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/a327627d881b/dvdy0241-0169-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/d2e197fa9c3e/dvdy0241-0169-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f6/3564404/07c1b426e690/dvdy0241-0169-f9.jpg

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