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

J Biol Chem. 2018 Mar 16;293(11):3937-3948. doi: 10.1074/jbc.RA117.000528. Epub 2018 Jan 30.


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.

Keywords: CCAAT-enhancer-binding protein (C/EBP); DNA repair; STAT transcription factor; Stat3; innate immunity; stress response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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


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