Stat3 and CCAAT enhancer–binding protein β (C/ebpβ) activate Fanconi C gene transcription during emergency granulopoiesis
| Autor: | Liping Hu, Ling Bei, Danielle B. Dressler, Larisa Broglie, Elizabeth A. Eklund, Weiqi Huang, Chirag A. Shah |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine congenital hereditary and neonatal diseases and abnormalities DNA Repair Transcription Genetic DNA damage DNA repair Sequence Homology Apoptosis Biology CCAAT-enhancer-binding protein (C/EBP) Biochemistry Granulopoiesis Mice 03 medical and health sciences Transcription (biology) hemic and lymphatic diseases Animals Humans Promoter Regions Genetic STAT3 innate immunity Molecular Biology Transcription factor STAT transcription factor Stat3 Base Sequence Ccaat-enhancer-binding proteins CCAAT-Enhancer-Binding Protein-beta Fanconi Anemia Complementation Group C Protein nutritional and metabolic diseases stress response U937 Cells Cell Biology DNA Repair Pathway Hematopoiesis 3. Good health Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Cancer research biology.protein Developmental Biology Granulocytes |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Popis: | Interferon consensus sequence–binding protein (Icsbp) is required for terminating emergency granulopoiesis, an episodic event responsible for granulocyte production in response to infections and a key component of the innate immune response. Icsbp inhibits the expression of Stat3 and C/ebpβ, transcription factors essential for initiating and sustaining granulopoiesis, and activates transcription of Fanconi C (FANCC), a DNA repair protein. In prior studies, we noted accelerated bone marrow failure in Fancc−/− mice undergoing multiple episodes of emergency granulopoiesis, associated with apoptosis of bone marrow cells with unrepaired DNA damage. Additionally, we found increased expression of Fanconi C and F proteins during emergency granulopoiesis. These findings suggest that Icsbp protects the bone marrow from DNA damage by increasing activity of the Fanconi DNA repair pathway, but the mechanisms for FANCC activation during initiation of emergency granulopoiesis are unclear. In this study, we observed that Stat3 and C/ebpβ activate FANCC transcription and contribute to DNA repair. Our findings indicate that FancC expression is increased during Stat3- and C/ebpβ-induced initiation of emergency granulopoiesis by these transcription factors and is maintained through termination by Icsbp. Our work reveals that Stat3- and C/ebpβ-mediated FancC expression is a critical component for initiating and sustaining key innate immune responses. |
| Databáze: | OpenAIRE |
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