CEBPE gene expression is enhanced by CEBPA, SPI1 (PU.1), and retinoic acid

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Reaction [omitted]
Homo sapiens
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CEBPE is expressed exclusively in myeloid progenitor cells and is required for terminal differentiation of granulocyte precursors. Transcription of CEBPE is activated by at least 3 mechanisms:
1) CEBPA dimers bound to the promoter of CEBPE (Yamanaka et al. 1997, Matusushita et al. 2008, Loke et al. 2018, and inferred from mouse homologs),
2) SPI1 (PU.1), PML. and EP300 bound to the promoter of CEBPE (Yoshida et al. 2007), and
3) retinoic acid activation of the RARA:RXR retinoic acid receptor bound to the CEBPE promoter (Park et al. 1999, Verbeek et al. 1999, Cai et al. 2010, Iriyama et al. 2014). Activation of CEBPE by retinoic acid is believed to ameliorate some cases of leukemia (Park et al. 1999).

Literature References
PubMed ID Title Journal Year
17562868 PML-retinoic acid receptor alpha inhibits PML IV enhancement of PU.1-induced C/EBPepsilon expression in myeloid differentiation

Pandolfi, PP, Naoe, T, Ichikawa, H, Akao, Y, Yoshida, H, Katsumoto, T, Ohnishi, K, Tagata, Y, Kitabayashi, I

Mol. Cell. Biol. 2007
18776924 C/EBPalpha and C/EBPvarepsilon induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene

Asai, S, Hotta, T, Tsukamoto, H, Nakamura, Y, Nosaka, T, Ando, K, Miyachi, H, Tanaka, Y, Hayashi, Y, Sugita, K, Matsushita, H, Jin, G, Nakajima, H, Ono, R, Yabe, M, Morimoto, A

Oncogene 2008
24379003 Enhancement of differentiation induction and upregulation of CCAAT/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid

Horikoshi, A, Takagi, N, Yoshino, Y, Toyoda, H, Takeuchi, J, Takei, M, Aizawa, S, Hatta, Y, Iriyama, N, Yuan, B

Int. J. Oncol. 2014
10233885 C/EBPepsilon directly interacts with the DNA binding domain of c-myb and cooperatively activates transcription of myeloid promoters

Verbeek, W, Müller, C, Friedman, AD, Koeffler, HP, Gombart, AF, Chumakov, AM

Blood 1999
9177240 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

Antonson, P, Xanthopoulos, KG, Smith, LT, Tenen, DG, Yamanaka, R, Radomska, HS, Lekstrom-Himes, J, Kim, GD

Proc. Natl. Acad. Sci. U.S.A. 1997
29431622 C/EBPα overrides epigenetic reprogramming by oncogenic transcription factors in acute myeloid leukemia

Pickin, A, Imperato, MR, Bonifer, C, Ptasinska, A, Cockerill, PN, Loke, J, Keane, P, Assi, SA, Chin, PS

Blood Adv 2018
20661648 C/EBPε participates in all-trans retinoic acid induction of PI3Kγ in U937 cells via an intronic matrix attachment region sequence

Xu, W, Chen, B, Cai, R, Lu, J, Cai, X

Mol. Biol. Rep. 2010
10330422 CCAAT/enhancer binding protein epsilon is a potential retinoid target gene in acute promyelocytic leukemia treatment

Vuong, PT, Park, DJ, Miller, WH, Koeffler, HP, Gombart, AF, Chih, DY, Chumakov, AM

J. Clin. Invest. 1999
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