CEBPE (CCAAT/enhancer binding protein epsilon)

2017-03-01   Thomas Burmeister 

Charite, Med. Klinik fur Hamatologie, Onkologie und Tumorimmunologie, Hindenburgdamm 30, 12200 Berlin, Germany;




Review on CEBPE, with data on DNA, on the protein encoded, and where the gene is implicated.


Atlas Image
Figure 1: Human CEBPE gene and mRNA transcript: a. according to the GRCh38.p7 assembly annotation (2016/03/21); b. according to Yamanaka et al. (1997); c. transcripts based on the Yamanaka exon organization


CEBPE is located on chromosome 14q11.2 in a telomer-centromer orientation. Conflicting data have been published on the gene structure of CEBPE. According to the GRCh38.p7 assembly annotation (2016/03/21) the gene consists of two exons (1030 bp and 517 bp), which are partially coding and separated by a 759 bp intron (Figure 1a).
This is in conflict with some previously published papers. Yamanaka et al. (1997) described an alternative 3-exon-organization of the human CEBPE gene (Figure 1b). However, exon 1, as described by Yamanaka et al. contains a frameshift according to the GRCh38.p7 NCBI assembly.


Various transcripts have been reported, resulting in four protein isoforms (Lekstrom-Himes 2001, Yamanaka 1997; Figure 1c). All transcripts share a common 3 end.



CEBPE is a member of the CCAAT/enhancer-binding protein (C/EBP) family, which also includes CEBPA, CEBPB, CEBPG, CEBPD and CEBPZ (Ramji & Foka; 2002). A common structural feature of the C/EBP proteins is the presence of a highly conserved 55-65 amino acid sequence at the C-terminus which encodes a basic leucine zipper motif (bZIP domain) that functions as a dimerization domain. In the aminoterminal part all C/EBP proteins possess a DNA-binding domain with relative specificity for the CCAAT DNA motif. C/EBP proteins exert their physiological functions as either homo- or heterodimers. They can also interact with other bZIP- and non-bZIP transcription factors. Different protein domains have been characterized. The full-length CEBPE protein basically consists of an activation domain at the aminoterminal end, a repression domain in the center and the leucine zipper at the carboxyterminus (Williamson et al. 1998).
At least four different CEBPE protein isoforms of 32, 30, 27, and 14 kDa have been described, but their functional significance is unclear (Lekstrom-Hines et al. 2001, Figure 1c).
The CEBPE translation product can undergo a number of post-translational modifications. Phosphorylation of CEBPE on threonine 75, located in the transactivation domain, is associated with increased DNA binding capacity and transcriptional activation (Williamson et al., 2005). Sumoylation of lysine residues within the repression domain has been found to modulate CEBPE function (Kim et al., 2005). Acetylation of lysine-121 and lysine-198 was found to be critical for terminal neutrophil differentiation (Bartels et. al., 2015).


CEBPE is predominantly expressed in cells of the hematopoietic system and to a much lesser extent in ovarian tissue (Yamanaka, et al., 1997). In normal hematopoietic cells CEBPE is preferentially expressed in myeloid-committed cells and the protein is virtually only detectable in metamyelocytes and myelocytes. The gene is also expressed in more immature myeloid cells but protein translation is repressed by miRNA-130a (Larsen et al., 2014). The expression of CEBPE protein induces growth arrest, morphological differentiation, secondary granule proteins and has proapoptotic effects (Nakajima et al. 2006).




CEBPE is a transcription factor, important for monocyte and granulocyte development. The transcription factor binds as a homodimer or heterodimer (with CEBPD) to specific DNA regulatory regions. Shorter CEBPE protein isoforms are hypothetical attenuators of the transcriptional activity of the long isoform.
Homozygous CEBPE knock-out (-/-) mice appear healthy at birth but survive only 2-5 months after birth, while heterozygous CEBPE knock-out mice appear normal. CEBPE (-/-) mice showed a marked increase in immature myeloid progenitors, increased numbers of morphologically abnormal neutrophils, that were functionally defect and lacked an oxidative burst, and decreased numbers of eosinophils. Thus it was concluded that CEBPE is essential for a normal terminal differentiation of committed granulocyte progenitor cells (Yamanaka, et al., 1997).

Implicated in

Entity name
Neutrophil specific granule deficiency (SGD)
Some, but not all of the very few known patients with SGD harboured CEBPE mutations which led to loss of the dimerization domain; phenotypically, SGD patients show bilobed nuclei, impaired chemotaxis and bactericidal activity with susceptibility to severe bacterial infections (Gombart & Koeffler 2002).
Entity name
Acute lymphoblastic leukemia (ALL)
The CEBPE single nucleotide polymorphism rs2239633 has been implicated as a susceptibility factor for the development of B lineage ALL in children and adults. The relative risk (odds ratio) conferred is 1.1-1.6 (Papaemmanuil et al., 2009; Burmeister et al. 2014).
Entity name
t(14;14)(q11;q32) CEBPE/IGH and inv(14)(q11q32) CEBPE/IGH
CEBPE is found recurrently translocated to the immunoglobulin heavy chain locus ( IGH) on 14q32 in acute lymphoblastic leukemia patients with inv(14)(q11q32)/t(14;14)(q11;q32). The translocation leads to an overexpression of CEBPE under the control of the immunoglobulin heavy chain gene promoters. At least five cases have been described (Akasaka et al. 2007).


Pubmed IDLast YearTitleAuthors
171701242007Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).Akasaka T et al
255683492015Acetylation of C/EBPε is a prerequisite for terminal neutrophil differentiation.Bartels M et al
244975672014Germline variants in IKZF1, ARID5B, and CEBPE as risk factors for adult-onset acute lymphoblastic leukemia: an analysis from the GMALL study group.Burmeister T et al
117530762002Neutrophil specific granule deficiency and mutations in the gene encoding transcription factor C/EBP(epsilon).Gombart AF et al
190274932008Translocation (14;14)(q11;q32) with simultaneous involvement of the IGH and CEBPE genes in B-lineage acute lymphoblastic leukemia.Han Y et al
156617392005Repression and coactivation of CCAAT/enhancer-binding protein epsilon by sumoylation and protein inhibitor of activated STATx proteins.Kim J et al
243983272014miRNA-130a regulates C/EBP-ε expression during granulopoiesis.Larsen MT et al
165314052006N-terminal region of CCAAT/enhancer-binding protein epsilon is critical for cell cycle arrest, apoptosis, and functional maturation during myeloid differentiation.Nakajima H et al
196846042009Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia.Papaemmanuil E et al
200427262010Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood.Prasad RB et al
120061032002CCAAT/enhancer-binding proteins: structure, function and regulation.Ramji DP et al
156775662005CCAAT/enhancer binding protein epsilon: changes in function upon phosphorylation by p38 MAP kinase.Williamson EA et al
91772401997CCAAT/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.Yamanaka R et al

Other Information

Locus ID:

NCBI: 1053
MIM: 600749
HGNC: 1836
Ensembl: ENSG00000092067


dbSNP: 1053
ClinVar: 1053
TCGA: ENSG00000092067


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
196846042009Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia.159
200427262010Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood.49
122024802002Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein.41
125157292003Regulation of neutrophil and eosinophil secondary granule gene expression by transcription factors C/EBP epsilon and PU.1.40
191091892009Inflammatory cytokine production by human neutrophils involves C/EBP transcription factors.29
188326582009Human C/EBP-epsilon activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation.21
123934502003CCAAT/Enhancer binding proteins repress the leukemic phenotype of acute myeloid leukemia.19
125220002003Chromatin immunoprecipitation (ChIP) studies indicate a role for CCAAT enhancer binding proteins alpha and epsilon (C/EBP alpha and C/EBP epsilon ) and CDP/cut in myeloid maturation-induced lactoferrin gene expression.18
172446862007Growth factor independence-1 (Gfi-1) plays a role in mediating specific granule deficiency (SGD) in a patient lacking a gene-inactivating mutation in the C/EBPepsilon gene.18
120368692002Induction of granulocytic differentiation by 2 pathways.17


Thomas Burmeister

CEBPE (CCAAT/enhancer binding protein epsilon)

Atlas Genet Cytogenet Oncol Haematol. 2017-03-01

Online version: