Modelling and identification of transcription-factor binding motifs in human chondrogenesis.

Yunlong Liu, H. Yokota

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Chondrogenesis is a dynamical process of cartilage formation involving many transcription factors and transcription-factor binding motifs (TFBMs). Using a series of microarray-derived mRNA profiles for human chondrogenesis, a computational model was built to identify critical TFBMs and model-driven prediction was evaluated experimentally using a promoter competition assay. First, the model was used to approximate the observed mRNA levels using frequencies of potential TFBMs which appeared in the regulatory DNA sequences. Potential TFBMs were chosen from a random population of 5-bp DNA fragments, and the selected genes included chondrocyte specific genes such as type II collagen. Using the Akaike information criterion and the genetic algorithm, six sets of putative TFBMs was chosen from the 5'-end flanking region encompassing 125-, 250-, 500-, and 1000-bp sequences. The minimum model error was obtained in the model with the 500-bp regulatory region. Second, the promoter competition assay was conducted for the selective collagen genes. The assay supported the stimulatory role of a novel TFBM (5'-AGGGG-3') in induction of type II and type III collagens.

Original languageEnglish (US)
Pages (from-to)85-92
Number of pages8
JournalSystems biology
Volume1
Issue number1
DOIs
StatePublished - Jun 2004
Externally publishedYes

Fingerprint

Chondrogenesis
Transcription factors
Transcription Factor
Transcription Factors
Collagen
Modeling
Assays
Collagen Type II
Genes
Gene
Promoter
Messenger RNA
Cartilage
Model Error
Akaike Information Criterion
Collagen Type III
5' Flanking Region
Nucleic Acid Regulatory Sequences
DNA sequences
Microarrays

ASJC Scopus subject areas

  • Modeling and Simulation
  • Biotechnology
  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Genetics

Cite this

Modelling and identification of transcription-factor binding motifs in human chondrogenesis. / Liu, Yunlong; Yokota, H.

In: Systems biology, Vol. 1, No. 1, 06.2004, p. 85-92.

Research output: Contribution to journalArticle

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