[Frontiers in Bioscience 7, a126-134, June 1, 2002]
SYSTEMS ANALYSIS OF MATRIX METALLOPROTEINASE MRNA EXPRESSION IN SKELETAL TISSUES
Lei Qian 1, Yunlong Liu 1, Hui Bin Sun 1,2, and Hiroki Yokota 1,2, 3
1Biomedical Engineering Program, 2 Departments of Anatomy and Cell Biology, and 3 Mechanical Engineering, Indiana University - Purdue University Indianapolis, Indianapolis, IN
TABLE OF CONTENTS
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.