Stat3 and CCAAT enhancer-binding protein β (C/ebpβ) activate Fanconi C gene transcription during emergency granulopoiesis.

Abstract

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.

• Authors: Chirag A Shah, Larisa Broglie, Liping Hu, Ling Bei, Weiqi Huang, Danielle B Dressler, Elizabeth A Eklund
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 293 Issue 11 Pg. 3937-3948 (03 16 2018) ISSN: 1083-351X [Electronic] United States
• PMID: 29382715 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• CCAAT-Enhancer-Binding Protein-beta
• CEBPB protein, human
• Cebpb protein, mouse
• Fanconi Anemia Complementation Group C Protein
• STAT3 Transcription Factor

Topics

• Animals
• Apoptosis
• Base Sequence
• CCAAT-Enhancer-Binding Protein-beta (genetics, metabolism)
• DNA Repair
• Fanconi Anemia Complementation Group C Protein (genetics, metabolism)
• Gene Expression Regulation
• Granulocytes (metabolism, pathology)
• Hematopoiesis
• Humans
• Mice
• Mice, Inbred C57BL
• Promoter Regions, Genetic
• STAT3 Transcription Factor (genetics, metabolism)
• Sequence Homology
• Transcription, Genetic
• U937 Cells