Systems analysis of matrix metalloproteinase mRNA expression in 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.
Qian
Lei
L
Biomedical Engineering Program, Purdue University Indianapolis, Indianapolis, IN, USA.
Liu
Yunlong
Y
Sun
Hui Bin
HB
Yokota
Hiroki
H
D000465:Algorithms; D001842:Bone and Bones / Q000201:enzymology*; D019295:Computational Biology / Q000379:methods* / Q000706:statistics & numerical data; D030541:Databases, Genetic; D004790:Enzyme Induction / Q000235:genetics; D004794:Enzyme Repression / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D016014:Linear Models; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D008957:Models, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis*; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic / Q000235:genetics
D012333:RNA, Messenger; D020782:Matrix Metalloproteinases