Systems analysis of matrix metalloproteinase mRNA expression in skeletal tissues
Systems analysis of matrix metalloproteinase mRNA expression in skeletal tissues
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DOI：
10.2741/qian
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发表时间：
2002-06-01
影响因子：
3.1
通讯作者：
Yokota, H
中科院分区：
文献类型：
--
作者：
Qian, L;Liu, YL;Yokota, H
人类基因组序列的可用性为生命科学家和生物医学工程师提供了一个具有挑战性的机会来开发用于定量分析生物过程的计算和实验工具。为了满足将实验 mRNA 表达数据与人类基因组序列整合的日益增长的需求，我们在此提出了一种名为“基于启动子的估计 (PROBE)”分析的独特分析。 PROBE 分析是使用控制和估计理论对转录过程进行“系统分析”。建立线性模型是为了根据一组基因的调控 DNA 序列估计其 mRNA 水平。该模型还用于解释骨骼组织中的两个独立数据集。结果表明，基质金属蛋白酶家族的 mRNA 水平可以根据调节 DNA 序列上顺式作用元件的分布进行建模。该模型准确预测了 AP1、NFY、PEA3 和 Sp1 等顺式作用元件的刺激作用以及 AP2 的抑制作用。这些预测与生物学观察结果一致，并且提出了用于测试此类预测的特定测定法。尽管真核转录是一个复杂的机制，但这里提供的两个例子支持了所描述的分析在阐明 DNA 调控元件的功能意义方面的潜在用途。
The availability of human genome sequences provides life scientists and biomedical engineers with a challenging opportunity to develop computational and experimental tools for quantitatively analyzing biological processes. In response to a growing need to integrate experimental mRNA expression data with human genome sequences, we present here a unique analysis named "Promoter-Based Estimation (PROBE)" analysis. The PROBE analysis is "systems analysis" of transcriptional processes using control and estimation theories. A linear model was built in order to estimate the mRNA levels of a group of genes from their regulatory DNA sequences. The model was also used to interpret two independent datasets in skeletal tissues. The results demonstrated that the mRNA levels of a family of matrix metalloproteinases can be modeled from a distribution of cis-acting elements on regulatory DNA sequences. The model accurately predicted a stimulatory role of cis-acting elements such as AP1, NFY, PEA3, and Sp1 as well as an inhibitory role of AP2. These predictions are consistent with biological observations, and a specific assay for testing such predictions is proposed. Although eukaryotic transcription is a complex mechanism, the two examples presented here support the potential use of the described analysis for elucidating the functional significance of DNA regulatory elements.