Premium
Combinatorial and Temporal Codes within pathogen‐responsive Gene Regulatory Networks
Author(s) -
Hoffmann Alexander
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.228.3
Subject(s) - computational biology , gene regulatory network , systems biology , biology , gene , gene expression , regulation of gene expression , transcription factor , computer science , transcriptome , promoter , genetics
How stimulus‐responsive gene expression is specified remains an important unresolved biological question. Studies of model gene promoters advanced the hypothesis of a Combinatorial Code of transcription factors (TFs), and recent observations of stimulus‐specific TF activation dynamics suggested the hypothesis of a Temporal Code. Neither hypothesis has been tested with mammalian transcriptome‐wide measurements, or integrated within a model of signal‐responsive gene regulatory networks (GRNs). Here, I will discuss our recent studies of the pathogen‐responsive gene expression program using the systems biology approach of iterative mathematical modeling and quantitative experimentation. Our findings indicate that predictive models for gene expression cannot be based on nuclear GRNs alone, but must also consider the cytoplasmic, dynamic Signal Regulatory Network (SRN). The described framework allows for the necessary integration of bottom‐up and top‐down systems biology approaches.