RRC ID 41822
Author Sun HB, Liu Y, Qian L, Yokota H.
Title Model-based analysis of matrix metalloproteinase expression under mechanical shear.
Journal Ann Biomed Eng
Abstract We report the development of a model-based analysis for identification of the role of transcription factor (TF) binding motifs. A nonlinear mathematical model was formulated to establish the quantitative relationship between the temporal expression profiles and the distribution of known TF binding motifs on regulatory DNA regions. In order to evaluate biological meaning of the nonlinear model, the role of TF binding motifs predicted by the model was examined by a promoter competition assay where specific TF binding motifs were inactivated by a transient transfer of the DNA fragments consisting of the TF binding motifs. Using the shear stress responses of a family of matrix metalloproteinases in human synovial cells as a model system, we showed that the nonlinear formulation was able to approximate the experimentally observed expression profile better than the linear formulation, and the stimulatory and inhibitory roles of TF binding motifs extracted from the model were validated by the competition assay. The results support that an integrated usage of the nonlinear model and the biochemical evaluation assay would contribute to identifying critical regulatory DNA elements in mechanical responses in connective tissue.
Volume 31(2)
Pages 171-80
Published 2003-2-1
DOI 10.1114/1.1540635
PMID 12627825
MeSH Amino Acid Motifs / genetics Amino Acid Motifs / physiology Computer Simulation DNA / genetics DNA / physiology Gene Expression Profiling / methods Gene Expression Regulation / genetics Gene Expression Regulation / physiology* Humans Linear Models Matrix Metalloproteinases / biosynthesis Matrix Metalloproteinases / genetics Matrix Metalloproteinases / physiology* Mechanotransduction, Cellular / genetics Mechanotransduction, Cellular / physiology* Models, Biological Models, Genetic* Nonlinear Dynamics Physical Stimulation / methods Protein Binding Regulatory Sequences, Nucleic Acid / genetics Sequence Analysis, DNA Shear Strength Stress, Mechanical Synovial Membrane / physiology* Transcription Factors / genetics Transcription Factors / physiology
IF 3.324
Times Cited 7
Human and Animal Cells MH7A(RCB1512)