Dataset Information
Begitt2014 - STAT1 cooperative DNA binding - single GAS polymer model
Ontology highlight
ABSTRACT: The importance of STAT1-cooperative DNA binding in type 1 and type 2 interferon signalling has been studies using experimental and modelling approaches. The authors have developed two ODE models to describe STAT1 binding to short promoter regions of DNA, namely "single GAS polymer model" and "double GAS polymer model" considering binding to single or double GAS sites, respectively. The length of DNA in the single GAS model was three sites and four sites in double GAS model. This model correspond to the "single GAS polymer model". This model is described in the article: Abstract: STAT1 is an indispensable component of a heterotrimer (ISGF3) and a STAT1 homodimer (GAF) that function as transcription regulators in type 1 and type 2 interferon signaling, respectively. To investigate the importance of STAT1-cooperative DNA binding, we generated gene-targeted mice expressing cooperativity-deficient STAT1 with alanine substituted for Phe77. Neither ISGF3 nor GAF bound DNA cooperatively in the STAT1F77A mouse strain, but type 1 and type 2 interferon responses were affected differently. Type 2 interferon-mediated transcription and antibacterial immunity essentially disappeared owing to defective promoter recruitment of GAF. In contrast, STAT1 recruitment to ISGF3 binding sites and type 1 interferon-dependent responses, including antiviral protection, remained intact. We conclude that STAT1 cooperativity is essential for its biological activity and underlies the cellular responses to type 2, but not type 1 interferon. This model is hosted on BioModels Database and identifiedby: BIOMD0000000500 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resourcefor published quantitative kinetic models . To the extent possible under law, all copyright and related orneighbouring rights to this encoded model have been dedicated to the publicdomain worldwide. Please refer to CC0 Public DomainDedication for more information.
ORGANISM(S): Mus musculus
SUBMITTER: Lucian Smith
PROVIDER: MODEL1311130001 | biostudies-other |
SECONDARY ACCESSION(S): 24413774
REPOSITORIES: biostudies-other
Publications
STAT1-cooperative DNA binding distinguishes type 1 from type 2 interferon signaling.
Nature immunology 20140112 2
STAT1 is an indispensable component of a heterotrimer (ISGF3) and a STAT1 homodimer (GAF) that function as transcription regulators in type 1 and type 2 interferon signaling, respectively. To investigate the importance of STAT1-cooperative DNA binding, we generated gene-targeted mice expressing cooperativity-deficient STAT1 with alanine substituted for Phe77. Neither ISGF3 nor GAF bound DNA cooperatively in the STAT1F77A mouse strain, but type 1 and type 2 interferon responses were affected diff ...[more]
