Dissection of a complex transcriptional response using genome-wide transcriptional modelling.
Mol Syst Biol
; 5: 327, 2009.
Article
em En
| MEDLINE
| ID: mdl-19920812
ABSTRACT
Modern genomics technologies generate huge data sets creating a demand for systems level, experimentally verified, analysis techniques. We examined the transcriptional response to DNA damage in a human T cell line (MOLT4) using microarrays. By measuring both mRNA accumulation and degradation over a short time course, we were able to construct a mechanistic model of the transcriptional response. The model predicted three dominant transcriptional activity profiles-an early response controlled by NFkappaB and c-Jun, a delayed response controlled by p53, and a late response related to cell cycle re-entry. The method also identified, with defined confidence limits, the transcriptional targets associated with each activity. Experimental inhibition of NFkappaB, c-Jun and p53 confirmed that target predictions were accurate. Model predictions directly explained 70% of the 200 most significantly upregulated genes in the DNA-damage response. Genome-wide transcriptional modelling (GWTM) requires no prior knowledge of either transcription factors or their targets. GWTM is an economical and effective method for identifying the main transcriptional activators in a complex response and confidently predicting their targets.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Genoma Humano
/
Modelos Genéticos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Syst Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Reino Unido