Systems analysis of matrix metalloproteinase mRNA expression in skeletal tissues.

Lei Qian, Yunlong Liu, Hui Bin Sun, Hiroki Yokota

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)a126-134
JournalFrontiers in bioscience : a journal and virtual library
Volume7
DOIs
StatePublished - Jun 1 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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