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Promoter Occupancy of STAT1 in Interferon Responses Is Regulated by Processive Transcription
- Source :
- Molecular and Cellular Biology. 35:716-727
- Publication Year :
- 2015
- Publisher :
- Informa UK Limited, 2015.
-
Abstract
- Interferons regulate immunity by inducing DNA binding of the transcription factor STAT1 through Y701 phosphorylation. Transcription by STAT1 needs to be restricted to minimize the adverse effects of prolonged immune responses. It remains unclear how STAT1 inactivation is regulated such that the transcription output is adequate. Here we show that efficient STAT1 inactivation in macrophages is coupled with processive transcription. Ongoing transcription feeds back to reduce the promoter occupancy of STAT1 and, consequently, the transcriptional output. Once released from the promoter, STAT1 is ultimately inactivated by Y701 dephosphorylation. We observe similar regulation for STAT2 and STAT3, suggesting a conserved inactivation mechanism among STATs. These findings reveal that STAT1 promoter occupancy in macrophages is regulated such that it decreases only after initiation of the transcription cycle. This feedback control ensures the fidelity of cytokine responses and provides options for pharmacological intervention.
- Subjects :
- Myxovirus Resistance Proteins
Transcription, Genetic
Primary Cell Culture
Response element
E-box
Mice
Sp3 transcription factor
Animals
RNA, Messenger
STAT1
Phosphorylation
Promoter Regions, Genetic
STAT3
Molecular Biology
Transcription factor
Cell Line, Transformed
Feedback, Physiological
Binding Sites
General transcription factor
biology
Macrophages
Interferon-beta
Articles
Cell Biology
Fibroblasts
Embryo, Mammalian
Molecular biology
Interferon-Stimulated Gene Factor 3, gamma Subunit
Cell biology
STAT1 Transcription Factor
Gene Expression Regulation
TAF2
biology.protein
Interferon Regulatory Factor-1
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....6f2830d235b4f64b4d4a3a4be68d56e3