IMR Press / FBL / Volume 7 / Issue 1 / DOI: 10.2741/qian

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Systems analysis of matrix metalloproteinase mRNA expression in skeletal tissues
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1 Biomedical Engineering Program, Indiana University - Purdue University Indianapolis, Indianapolis, IN
2 Departments of Anatomy and Cell Biology, Indiana University - Purdue University Indianapolis, Indianapolis, IN
3 Mechanical Engineering, Indiana University - Purdue University Indianapolis, Indianapolis, IN
Academic Editor:Jeremy Mao
Front. Biosci. (Landmark Ed) 2002, 7(1), 126–134;
Published: 1 June 2002
(This article belongs to the Special Issue Biomimetics and engineering of skeletal tissues)

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.

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