Gene Symbol: Cebpe
Description: CCAAT/enhancer binding protein (C/EBP), epsilon
Alias: C/EBPe, C/EBPepsilon, CRP1, Gm294, CCAAT/enhancer-binding protein epsilon, C/EBP-related protein 1
Species: mouse
Products:     Cebpe

Top Publications

  1. Williams S, Du Y, Schwartz R, Weiler S, Ortiz M, Keller J, et al. C/EBPepsilon is a myeloid-specific activator of cytokine, chemokine, and macrophage-colony-stimulating factor receptor genes. J Biol Chem. 1998;273:13493-501 pubmed
    ..These results suggest that C/EBPepsilon may be an important regulator of differentiation of a subset of myeloid cell types and may also participate in the regulation of cytokine gene expression in mature cells. ..
  2. Tagata Y, Yoshida H, Nguyen L, Kato H, Ichikawa H, Tashiro F, et al. Phosphorylation of PML is essential for activation of C/EBP epsilon and PU.1 to accelerate granulocytic differentiation. Leukemia. 2008;22:273-80 pubmed
    ..1-induced granulocytic differentiation. These results suggest that phosphorylation plays essential roles in the regulation of PML to accelerate granulocytic differentiation through multiple pathways. ..
  3. Gombart A, Kwok S, Anderson K, Yamaguchi Y, Torbett B, Koeffler H. Regulation of neutrophil and eosinophil secondary granule gene expression by transcription factors C/EBP epsilon and PU.1. Blood. 2003;101:3265-73 pubmed
    ..Furthermore, it indicates the importance of PU.1 in the cooperative activation of eosinophil granule genes. ..
  4. Tavor S, Vuong P, Park D, Gombart A, Cohen A, Koeffler H. Macrophage functional maturation and cytokine production are impaired in C/EBP epsilon-deficient mice. Blood. 2002;99:1794-801 pubmed
    ..Taken together, this study implicates the C/EBP epsilon gene as an important transcription factor required for normal function and development of macrophages. ..
  5. Yamanaka R, Barlow C, Lekstrom Himes J, Castilla L, Liu P, Eckhaus M, et al. Impaired granulopoiesis, myelodysplasia, and early lethality in CCAAT/enhancer binding protein epsilon-deficient mice. Proc Natl Acad Sci U S A. 1997;94:13187-92 pubmed
    ..Thus, C/EBP epsilon is essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells. ..
  6. Verbeek W, Wachter M, Lekstrom Himes J, Koeffler H. C/EBPepsilon -/- mice: increased rate of myeloid proliferation and apoptosis. Leukemia. 2001;15:103-11 pubmed
    ..C/EBPepsilon may have a role in the inhibition of apoptosis in maturing granulocytic cells. ..
  7. Tanaka M, Gombart A, Koeffler H, Shiohara M. Expression of bactericidal/permeability-increasing protein requires C/EBP epsilon. Int J Hematol. 2007;85:304-11 pubmed
    ..Expression of BPI in human cord blood cells was increased by incubation with 10-7 MATRA for 48 hours. These results demonstrate the requirement for C/EBP epsilon in mediating BPI gene expression in myeloid cells in vitro and in vivo. ..
  8. Gombart A, Krug U, O Kelly J, An E, Vegesna V, Koeffler H. Aberrant expression of neutrophil and macrophage-related genes in a murine model for human neutrophil-specific granule deficiency. J Leukoc Biol. 2005;78:1153-65 pubmed
    ..In summary, dysregulation of numerous, novel C/EBPepsilon target genes impairs innate immune response and possibly other important biological processes mediated by neutrophils and macrophages. ..
  9. Gery S, Gombart A, Fung Y, Koeffler H. C/EBPepsilon interacts with retinoblastoma and E2F1 during granulopoiesis. Blood. 2004;103:828-35 pubmed
    b>CCAAT enhancer binding protein epsilon (C/EBPepsilon) is a myeloid specific transcription factor that is essential for terminal granulocytic differentiation...

More Information


  1. Lekstrom Himes J, Xanthopoulos K. CCAAT/enhancer binding protein epsilon is critical for effective neutrophil-mediated response to inflammatory challenge. Blood. 1999;93:3096-105 pubmed
    ..Similarities between the C/EBPepsilon-deficient mouse model and the human disease, specific granule deficiency, will be discussed. ..
  2. Glenthøj A, Dahl S, Larsen M, Cowland J, Borregaard N. Human ?-defensin expression is not dependent on CCAAT/enhancer binding protein-? in a murine model. PLoS ONE. 2014;9:e92471 pubmed publisher
    ..We therefore crossed a transgenic HNP-1-expressing mouse with the Cebpe-/- mouse to study the in vivo significance of C/EBP-? for HNP-1 transcription and expression...
  3. Jenkins N, Gilbert D, Cho B, Strobel M, Williams S, Copeland N, et al. Mouse chromosomal location of the CCAAT/enhancer binding proteins C/EBP beta (Cebpb), C/EBP delta (Cebpd), and CRP1 (Cebpe). Genomics. 1995;28:333-6 pubmed
    ..known members of the C/EBP family of basic region-leucine zipper transcription factors: Cebpa, Cebpb, Cebpd, and Cebpe. Cebpa has previously been mapped to mouse chromosome 7...
  4. Khanna Gupta A, Zibello T, Idone V, Sun H, Lekstrom Himes J, Berliner N. Human neutrophil collagenase expression is C/EBP-dependent during myeloid development. Exp Hematol. 2005;33:42-52 pubmed
  5. Saisanit S, Sun X. Regulation of the pro-B-cell-specific enhancer of the Id1 gene involves the C/EBP family of proteins. Mol Cell Biol. 1997;17:844-50 pubmed
    ..We also demonstrate that CHOP is associated with C/EBPbeta in WEHI-231 cells, which may provide an additional mechanism to control the function of C/EBPbeta and the expression of the Id1 gene. ..
  6. Halene S, Gaines P, Sun H, Zibello T, Lin S, Khanna Gupta A, et al. C/EBPepsilon directs granulocytic-vs-monocytic lineage determination and confers chemotactic function via Hlx. Exp Hematol. 2010;38:90-103 pubmed publisher
    Mutations in the CCAAT enhancer binding protein epsilon (C/EBPepsilon) gene have been identified in the cells of patients with neutrophil specific granule deficiency, a rare congenital disorder marked by recurrent bacterial infections...
  7. Hu B, Wu Z, Nakashima T, Phan S. Mesenchymal-specific deletion of C/EBP? suppresses pulmonary fibrosis. Am J Pathol. 2012;180:2257-67 pubmed publisher
    ..Thus, these findings indicate an essential role for C/EBP? in the mesenchymal compartment in pulmonary fibrosis that is independent of its effects on inflammation or immune cell infiltration. ..
  8. Jones H, Yoo J, Crother T, Kyme P, Ben Shlomo A, Khalafi R, et al. Nicotinamide exacerbates hypoxemia in ventilator-induced lung injury independent of neutrophil infiltration. PLoS ONE. 2015;10:e0123460 pubmed publisher
    ..expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury...
  9. Akagi T, Thoennissen N, George A, Crooks G, Song J, Okamoto R, et al. In vivo deficiency of both C/EBP? and C/EBP? results in highly defective myeloid differentiation and lack of cytokine response. PLoS ONE. 2010;5:e15419 pubmed publisher
  10. Evrard M, Kwok I, Chong S, Teng K, Becht E, Chen J, et al. Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions. Immunity. 2018;48:364-379.e8 pubmed publisher
    ..In summary, our study identifies specialized BM granulocytic populations that ensure supply under homeostasis and stress responses. ..
  11. Nakajima H, Watanabe N, Shibata F, Kitamura T, Ikeda Y, Handa M. N-terminal region of CCAAT/enhancer-binding protein epsilon is critical for cell cycle arrest, apoptosis, and functional maturation during myeloid differentiation. J Biol Chem. 2006;281:14494-502 pubmed
    ..These data indicate the N terminus of C/EBPepsilon to be solely responsible for most aspects of myeloid differentiation, and these events were differentially affected by c-Myc. ..
  12. Takiguchi M. The C/EBP family of transcription factors in the liver and other organs. Int J Exp Pathol. 1998;79:369-91 pubmed
    ..Recent progress in clarification of regulatory mechanisms for the C/EBP family members gives insight into understanding the liver functions at the molecular level. ..
  13. Safar J, Prusiner S. Molecular studies of prion diseases. Prog Brain Res. 1998;117:421-34 pubmed
  14. Cohen T, Klarmann K, Sakchaisri K, Cooper J, Kuhns D, Anver M, et al. The lamin B receptor under transcriptional control of C/EBPepsilon is required for morphological but not functional maturation of neutrophils. Hum Mol Genet. 2008;17:2921-33 pubmed publisher
    ..Our findings indicate that the Lbr(GT/GT) mice are a model for Pelger-Huët anomaly and that Lbr, under transcriptional regulation of C/EBPepsilon, is necessary for morphological but not necessarily functional granulocyte maturation. ..
  15. Verbeek W, Lekstrom Himes J, Park D, Dang P, Vuong P, Kawano S, et al. Myeloid transcription factor C/EBPepsilon is involved in the positive regulation of lactoferrin gene expression in neutrophils. Blood. 1999;94:3141-50 pubmed
    ..In summary, our data implicate C/EBPepsilon as a critical factor of host antimicrobial defense and suggests that it has a direct role as a positive regulator of expression of lactoferrin in vivo. ..
  16. Kyme P, Thoennissen N, Tseng C, Thoennissen G, Wolf A, Shimada K, et al. C/EBP? mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. J Clin Invest. 2012;122:3316-29 pubmed publisher
    ..Nicotinamide was efficacious in both prophylactic and therapeutic settings. Our findings suggest that C/EBP? is an important target to boost killing of bacteria by the innate immune system. ..
  17. Liu Z, Petersen R, DEVIREDDY L. Impaired neutrophil function in 24p3 null mice contributes to enhanced susceptibility to bacterial infections. J Immunol. 2013;190:4692-706 pubmed publisher
    ..Therefore, the heightened sensitivity of 24p3(-/-) mice to these pathogens is not due to sequestration of siderophores limiting iron availability, but is a consequence of impaired neutrophil function...
  18. Okamoto R, Gery S, Gombart A, Wang X, Castellani L, Akagi T, et al. Deficiency of CCAAT/enhancer binding protein-epsilon reduces atherosclerotic lesions in LDLR-/- mice. PLoS ONE. 2014;9:e85341 pubmed publisher
    ..In this study, we generated Ldlr and Cebpe double-knockout (llee) mice and compared their atherogenic phenotypes to Ldlr single deficient (llEE) mice after ..
  19. Zheng Y, Zhang H, Wang Y, Li X, Lu P, Dong F, et al. Loss of Dnmt3b accelerates MLL-AF9 leukemia progression. Leukemia. 2016;30:2373-2384 pubmed publisher
    ..Taken together, these results demonstrate that Dnmt3b plays a tumor suppressive role in MLL-AF9 AML progression, thereby providing new insights into the roles of DNA methylation in leukemia development. ..
  20. Yamanaka R, Kim G, Radomska H, Lekstrom Himes J, Smith L, Antonson P, et al. CCAAT/enhancer binding protein epsilon is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of promoters and differential splicing. Proc Natl Acad Sci U S A. 1997;94:6462-7 pubmed
    ..3-kDa protein is not. Thus, C/EBPepsilon is regulated in a complex fashion and may play a role in the regulation of genes involved in myeloid differentiation. ..
  21. Yoshida H, Ichikawa H, Tagata Y, Katsumoto T, Ohnishi K, Akao Y, et al. PML-retinoic acid receptor alpha inhibits PML IV enhancement of PU.1-induced C/EBPepsilon expression in myeloid differentiation. Mol Cell Biol. 2007;27:5819-34 pubmed
    ..1/PML IV/p300 complex and inhibited PU.1-induced transcription. These results suggest a novel pathogenic mechanism of the PML-retinoic acid receptor alpha fusion protein in acute promyelocytic leukemia. ..
  22. Zhuang D, Qiu Y, Kogan S, Dong F. Increased CCAAT enhancer-binding protein epsilon (C/EBPepsilon) expression and premature apoptosis in myeloid cells expressing Gfi-1 N382S mutant associated with severe congenital neutropenia. J Biol Chem. 2006;281:10745-51 pubmed
  23. Paul F, Arkin Y, Giladi A, Jaitin D, Kenigsberg E, Keren Shaul H, et al. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors. Cell. 2015;163:1663-77 pubmed publisher
    ..These data establish a reference model and general framework for studying hematopoiesis at single-cell resolution. ..
  24. Chumakov A, Kubota T, Walter S, Koeffler H. Identification of murine and human XCP1 genes as C/EBP-epsilon-dependent members of FIZZ/Resistin gene family. Oncogene. 2004;23:3414-25 pubmed
    The CCAAT enhancer binding protein epsilon (C/EBP-epsilon) transcription factor is expressed predominantly in granulocytes. Mice with a disruption of the C/EBP-epsilon gene fail to produce mature granulocytes and eosinophils...
  25. Karamitros D, Patmanidi A, Kotantaki P, Potocnik A, Bähr Ivacevic T, Benes V, et al. Geminin deletion increases the number of fetal hematopoietic stem cells by affecting the expression of key transcription factors. Development. 2015;142:70-81 pubmed publisher
    ..Our data suggest that geminin is indispensable for fetal hematopoiesis and regulates the generation of a physiological pool of stem and progenitor cells in the fetal hematopoietic system. ..