CEBPE explained

CCAAT/enhancer binding protein (C/EBP), epsilon, also known as CEBPE and CRP1, is a type of ccaat-enhancer-binding protein. CEBPE is its human gene^{[1] [2]} and is pro-apoptotic.^[3]

The protein encoded by this gene is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related protein CEBP-δ. The encoded protein may be essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells. Mutations in this gene have been associated with specific granule deficiency, a rare congenital disorder. Multiple variants of this gene have been described, but the full-length nature of only one has been determined.^[4]

Further reading

• Sladek FM, Darnell JE . Mechanisms of liver-specific gene expression . Current Opinion in Genetics & Development . 2 . 2 . 256–9 . Apr 1992 . 1638120 . 10.1016/S0959-437X(05)80282-5 .
• Gombart AF, Koeffler HP . Neutrophil specific granule deficiency and mutations in the gene encoding transcription factor C/EBP(epsilon) . Current Opinion in Hematology . 9 . 1 . 36–42 . Jan 2002 . 11753076 . 10.1097/00062752-200201000-00007 . 25411864 .
• Williams SC, Cantwell CA, Johnson PF . A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro . Genes & Development . 5 . 9 . 1553–67 . Sep 1991 . 1884998 . 10.1101/gad.5.9.1553 . free .
• Antonson P, Stellan B, Yamanaka R, Xanthopoulos KG . A novel human CCAAT/enhancer binding protein gene, C/EBPepsilon, is expressed in cells of lymphoid and myeloid lineages and is localized on chromosome 14q11.2 close to the T-cell receptor alpha/delta locus . Genomics . 35 . 1 . 30–8 . Jul 1996 . 8661101 . 10.1006/geno.1996.0319 .
• Chumakov AM, Grillier I, Chumakova E, Chih D, Slater J, Koeffler HP . Cloning of the novel human myeloid-cell-specific C/EBP-epsilon transcription factor . Molecular and Cellular Biology . 17 . 3 . 1375–86 . Mar 1997 . 9032264 . 231862 . 10.1128/mcb.17.3.1375.
• Yamanaka R, Kim GD, Radomska HS, Lekstrom-Himes J, Smith LT, Antonson P, Tenen DG, Xanthopoulos KG . 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 . Proceedings of the National Academy of Sciences of the United States of America . 94 . 12 . 6462–7 . Jun 1997 . 9177240 . 21072 . 10.1073/pnas.94.12.6462 . free .
• Verbeek W, Gombart AF, Chumakov AM, Müller C, Friedman AD, Koeffler HP . C/EBPepsilon directly interacts with the DNA binding domain of c-myb and cooperatively activates transcription of myeloid promoters . Blood . 93 . 10 . 3327–37 . May 1999 . 10233885 . 10.1182/blood.V93.10.3327. free .
• Lekstrom-Himes JA, Dorman SE, Kopar P, Holland SM, Gallin JI . Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT/enhancer binding protein epsilon . The Journal of Experimental Medicine . 189 . 11 . 1847–52 . Jun 1999 . 10359588 . 2193089 . 10.1084/jem.189.11.1847 .
• Tavor S, Vuong PT, Park DJ, Gombart AF, Cohen AH, Koeffler HP . Macrophage functional maturation and cytokine production are impaired in C/EBP epsilon-deficient mice . Blood . 99 . 5 . 1794–801 . Mar 2002 . 11861297 . 10.1182/blood.V99.5.1794 . free .
• Zhang P, Nelson E, Radomska HS, Iwasaki-Arai J, Akashi K, Friedman AD, Tenen DG . Induction of granulocytic differentiation by 2 pathways . Blood . 99 . 12 . 4406–12 . Jun 2002 . 12036869 . 10.1182/blood.V99.12.4406 . free .
• Kim J, Cantwell CA, Johnson PF, Pfarr CM, Williams SC . Transcriptional activity of CCAAT/enhancer-binding proteins is controlled by a conserved inhibitory domain that is a target for sumoylation . The Journal of Biological Chemistry . 277 . 41 . 38037–44 . Oct 2002 . 12161447 . 10.1074/jbc.M207235200 . free .
• Du J, Stankiewicz MJ, Liu Y, Xi Q, Schmitz JE, Lekstrom-Himes JA, Ackerman SJ . Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein . The Journal of Biological Chemistry . 277 . 45 . 43481–94 . Nov 2002 . 12202480 . 10.1074/jbc.M204777200 . free .
• Truong BT, Lee YJ, Lodie TA, Park DJ, Perrotti D, Watanabe N, Koeffler HP, Nakajima H, Tenen DG, Kogan SC . CCAAT/Enhancer binding proteins repress the leukemic phenotype of acute myeloid leukemia . Blood . 101 . 3 . 1141–8 . Feb 2003 . 12393450 . 10.1182/blood-2002-05-1374 .
• Gombart AF, Kwok SH, Anderson KL, Yamaguchi Y, Torbett BE, Koeffler HP . Regulation of neutrophil and eosinophil secondary granule gene expression by transcription factors C/EBP epsilon and PU.1 . Blood . 101 . 8 . 3265–73 . Apr 2003 . 12515729 . 10.1182/blood-2002-04-1039 . free .
• Khanna-Gupta A, Zibello T, Sun H, Gaines P, Berliner N . Chromatin 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 . Blood . 101 . 9 . 3460–8 . May 2003 . 12522000 . 10.1182/blood-2002-09-2767 . free .
• Gery S, Gombart AF, Fung YK, Koeffler HP . C/EBPepsilon interacts with retinoblastoma and E2F1 during granulopoiesis . Blood . 103 . 3 . 828–35 . Feb 2004 . 12947005 . 10.1182/blood-2003-01-0159 .
• Gery S, Park DJ, Vuong PT, Chih DY, Lemp N, Koeffler HP . Retinoic acid regulates C/EBP homologous protein expression (CHOP), which negatively regulates myeloid target genes . Blood . 104 . 13 . 3911–7 . Dec 2004 . 15308577 . 10.1182/blood-2003-10-3688 . free .

Notes and References

1. Web site: Entrez Gene: CEBPE CCAAT/enhancer binding protein (C/EBP), epsilon.
2. Antonson P, Stellan B, Yamanaka R, Xanthopoulos KG . A novel human CCAAT/enhancer binding protein gene, C/EBPepsilon, is expressed in cells of lymphoid and myeloid lineages and is localized on chromosome 14q11.2 close to the T-cell receptor alpha/delta locus . Genomics . 35 . 1 . 30–8 . Jul 1996 . 8661101 . 10.1006/geno.1996.0319 .
3. 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 . The Journal of Biological Chemistry . 281 . 20 . 14494–502 . May 2006 . 16531405 . 10.1074/jbc.M600575200 . free .
4. Web site: Entrez Gene: CEBPE CCAAT/enhancer binding protein (C/EBP), epsilon.