| 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
|
|
WOS Category
|
ENGINEERING, BIOMEDICAL
|
| Resource |
| Human and Animal Cells |
MH7A(RCB1512) |
