Genomes and Genes
Gene Symbol: Cebpa
Description: CCAAT/enhancer binding protein (C/EBP), alpha
Alias: C/ebpalpha, CBF-A, Cebp, CCAAT/enhancer-binding protein alpha, C/EBP alpha
- Suh H, Gooya J, Renn K, Friedman A, Johnson P, Keller J. C/EBPalpha determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation. Blood. 2006;107:4308-16 pubmed..Thus, C/EBPalpha functions in hematopoietic cell fate decisions by the dual actions of inhibiting erythroid and inducing myeloid gene expression in multipotential progenitors. ..
- Schmidt D, Wilson M, Ballester B, Schwalie P, Brown G, Marshall A, et al. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science. 2010;328:1036-40 pubmed publisher..Our results reveal large interspecies differences in transcriptional regulation and provide insight into regulatory evolution. ..
- Davies N, Austen D, Wilde M, Darlington G, Brownlee G. Clotting factor IX levels in C/EBP alpha knockout mice. Br J Haematol. 1997;99:578-9 pubmed..We now report that mice homozygous for the deletion of the c/ebp alpha gene are significantly deficient in factor IX transcription. ..
- Yoon K, Smart R. C/EBPalpha is a DNA damage-inducible p53-regulated mediator of the G1 checkpoint in keratinocytes. Mol Cell Biol. 2004;24:10650-60 pubmed..Our results uncover a novel role for C/EBPalpha as a p53-regulated DNA damage-inducible gene that has a critical function in the DNA damage G(1) checkpoint response in keratinocytes. ..
- Zhang H, Alberich Jorda M, Amabile G, Yang H, Staber P, Di Ruscio A, et al. Sox4 is a key oncogenic target in C/EBP? mutant acute myeloid leukemia. Cancer Cell. 2013;24:575-88 pubmed publisher..Our data demonstrate that Sox4 overexpression resulting from C/EBP? inactivation contributes to the development of leukemia with a distinct LIC phenotype. ..
- Wang G, Shi X, Salisbury E, Sun Y, Albrecht J, Smith R, et al. Cyclin D3 maintains growth-inhibitory activity of C/EBPalpha by stabilizing C/EBPalpha-cdk2 and C/EBPalpha-Brm complexes. Mol Cell Biol. 2006;26:2570-82 pubmed..The inhibition of cyclin D3 blocks the formation of these complexes. Thus, these studies provide a new function of cyclin D3, which is to support the growth-inhibitory activity of C/EBPalpha. ..
- Timchenko N, Harris T, Wilde M, Bilyeu T, Burgess Beusse B, Finegold M, et al. CCAAT/enhancer binding protein alpha regulates p21 protein and hepatocyte proliferation in newborn mice. Mol Cell Biol. 1997;17:7353-61 pubmed
- Porse B, Pedersen T, Hasemann M, Schuster M, Kirstetter P, Luedde T, et al. The proline-histidine-rich CDK2/CDK4 interaction region of C/EBPalpha is dispensable for C/EBPalpha-mediated growth regulation in vivo. Mol Cell Biol. 2006;26:1028-37 pubmed..Homozygous Cebpa(DeltaPHR/DeltaPHR) (DeltaPHR) mice, carrying a modified cebpa allele lacking amino acids 180 to 194, were born at ..
- Simmons D, Natale D, Begay V, Hughes M, Leutz A, Cross J. Early patterning of the chorion leads to the trilaminar trophoblast cell structure in the placental labyrinth. Development. 2008;135:2083-91 pubmed publisher..5-14.5) including Ctsq in S-TGCs (also Hand1-positive), Syna in syncytiotrophoblast layer I (SynT-I), and Gcm1, Cebpa and Synb in syncytiotrophoblast layer II (SynT-II)...
- Muller C, Calkhoven C, Sha X, Leutz A. The CCAAT enhancer-binding protein alpha (C/EBPalpha) requires a SWI/SNF complex for proliferation arrest. J Biol Chem. 2004;279:7353-8 pubmed
- Johnson P. Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors. J Cell Sci. 2005;118:2545-55 pubmed..Other C/EBP-family members have also been implicated in positive and negative control of cell proliferation, and the mechanisms underlying their growth-regulatory activities are beginning to be elucidated. ..
- Wagner K, Zhang P, Rosenbauer F, Drescher B, Kobayashi S, Radomska H, et al. Absence of the transcription factor CCAAT enhancer binding protein alpha results in loss of myeloid identity in bcr/abl-induced malignancy. Proc Natl Acad Sci U S A. 2006;103:6338-43 pubmedThe lineage-determining transcription factor CCAAT enhancer binding protein alpha (C/EBPalpha) is required for myeloid differentiation. Decreased function or expression of C/EBPalpha is often found in human acute myeloid leukemia...
- Martis P, Whitsett J, Xu Y, Perl A, Wan H, Ikegami M. C/EBPalpha is required for lung maturation at birth. Development. 2006;133:1155-64 pubmed..Deletion of the Cebpa gene in respiratory epithelial cells in fetal mice caused respiratory failure at birth...
- Ross S, Radomska H, Wu B, Zhang P, Winnay J, Bajnok L, et al. Phosphorylation of C/EBPalpha inhibits granulopoiesis. Mol Cell Biol. 2004;24:675-86 pubmed..Thus, myeloid development is partly regulated by an ERK1/2-mediated change in the conformation of C/EBPalpha that favors monocyte differentiation by blocking granulopoiesis. ..
- Bereshchenko O, Mancini E, Moore S, Bilbao D, Mansson R, Luc S, et al. Hematopoietic stem cell expansion precedes the generation of committed myeloid leukemia-initiating cells in C/EBPalpha mutant AML. Cancer Cell. 2009;16:390-400 pubmed publisherWe here use knockin mutagenesis in the mouse to model the spectrum of acquired CEBPA mutations in human acute myeloid leukemia...
- Wang H, Goode T, Iakova P, Albrecht J, Timchenko N. C/EBPalpha triggers proteasome-dependent degradation of cdk4 during growth arrest. EMBO J. 2002;21:930-41 pubmed..Our studies show that C/EBPalpha disrupts the cdk4-cdc37-Hsp90 complex via direct interaction with cdk4 and reduces protein levels of cdk4 by increasing proteasome-dependent degradation of cdk4. ..
- Bengoechea Alonso M, Ericsson J. The ubiquitin ligase Fbxw7 controls adipocyte differentiation by targeting C/EBPalpha for degradation. Proc Natl Acad Sci U S A. 2010;107:11817-22 pubmed publisher..Thus, Fbxw7 could be an important regulator of energy and lipid metabolism. ..
- Croniger C, Trus M, Lysek Stupp K, Cohen H, Liu Y, Darlington G, et al. Role of the isoforms of CCAAT/enhancer-binding protein in the initiation of phosphoenolpyruvate carboxykinase (GTP) gene transcription at birth. J Biol Chem. 1997;272:26306-12 pubmed..We conclude that C/EBPalpha is required for the cAMP induction of PEPCK gene expression in the liver and that C/EBPbeta can compensate for the loss of C/EBPalpha if its concentration is induced to appropriate levels. ..
- Bararia D, Trivedi A, Zada A, Greif P, Mulaw M, Christopeit M, et al. Proteomic identification of the MYST domain histone acetyltransferase TIP60 (HTATIP) as a co-activator of the myeloid transcription factor C/EBPalpha. Leukemia. 2008;22:800-7 pubmed publisherThe transcription factor C/EBPalpha (CEBPA) is a key player in granulopoiesis and leukemogenesis. We have previously reported the interaction of C/EBPalpha with other proteins (utilizing mass spectrometry) in transcriptional regulation...
- Mancini E, Sanjuan Pla A, Luciani L, Moore S, Grover A, Zay A, et al. FOG-1 and GATA-1 act sequentially to specify definitive megakaryocytic and erythroid progenitors. EMBO J. 2012;31:351-65 pubmed publisher..Finally, C/EBPs and FOG-1 exhibited transcriptional cross-regulation in early myelo-erythroid progenitors making their functional antagonism a potential mechanism for separation of the myeloid and Mk/E lineages. ..
- Heath V, Suh H, Holman M, Renn K, Gooya J, Parkin S, et al. C/EBPalpha deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo. Blood. 2004;104:1639-47 pubmed..These findings show that C/EBPalpha deficiency results in hyperproliferation of HPCs and a block in the ability of multipotential progenitors to differentiate into bipotential granulocyte/macrophage progenitors and their progeny. ..
- Tanaka T, Yoshida N, Kishimoto T, Akira S. Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. EMBO J. 1997;16:7432-43 pubmed
- Hasemann M, Damgaard I, Schuster M, Theilgaard Monch K, Sørensen A, Mrsic A, et al. Mutation of C/EBPalpha predisposes to the development of myeloid leukemia in a retroviral insertional mutagenesis screen. Blood. 2008;111:4309-21 pubmed publisherThe CCAAT enhancer binding protein alpha (C/EBPalpha) is an important myeloid tumor suppressor that is frequently mutated in human acute myeloid leukemia (AML)...
- Christy R, Kaestner K, Geiman D, Lane M. CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A. 1991;88:2593-7 pubmed..The factor present in differentiated cells that binds at this site was identified as C/EBP (possibly in heterodimeric form with a homologous leucine-zipper protein), suggesting that C/EBP may regulate expression of its own gene. ..
- Maytin E, Lin J, Krishnamurthy R, Batchvarova N, Ron D, Mitchell P, et al. Keratin 10 gene expression during differentiation of mouse epidermis requires transcription factors C/EBP and AP-2. Dev Biol. 1999;216:164-81 pubmed..In response to differentiation signals, loss of AP-2 expression leads to derepression of the c/ebpalpha promoter and activation of k10 as cells migrate upward. ..
- Pedersen T, Bereshchenko O, Garcia Silva S, Ermakova O, Kurz E, Mandrup S, et al. Distinct C/EBPalpha motifs regulate lipogenic and gluconeogenic gene expression in vivo. EMBO J. 2007;26:1081-93 pubmed
- Flodby P, Barlow C, Kylefjord H, Ahrlund Richter L, Xanthopoulos K. Increased hepatic cell proliferation and lung abnormalities in mice deficient in CCAAT/enhancer binding protein alpha. J Biol Chem. 1996;271:24753-60 pubmed..These results suggest a critical role for C/EBPalpha in vivo for the acquisition of terminally differentiated functions in liver including the maintenance of physiologic energy homeostasis. ..
- Samuelsson L, Stromberg K, Vikman K, Bjursell G, Enerback S. The CCAAT/enhancer binding protein and its role in adipocyte differentiation: evidence for direct involvement in terminal adipocyte development. EMBO J. 1991;10:3787-93 pubmed..These findings strongly support the view that C/EBP is a necessary component of terminal adipocyte differentiation. ..
- Cao Z, Umek R, McKnight S. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991;5:1538-52 pubmed..The temporal pattern of expression of these three C/EBP isoforms during adipocyte differentiation may reflect the underpinnings of a regulatory cascade that controls the process of terminal cell differentiation. ..
- Roos A, Berg T, Barton J, Didon L, Nord M. Airway epithelial cell differentiation during lung organogenesis requires C/EBP? and C/EBP?. Dev Dyn. 2012;241:911-23 pubmed publisher..differentiation was assessed in mice with a lung epithelial-specific (SFTPC-Cre-mediated) deletion of C/EBP? (Cebpa(?LE) ), C/EBP? (Cebpb(?LE) ), or both genes (Cebpa(?LE) ; Cebpb(?LE) )...
- Fukuchi Y, Ito M, Shibata F, Kitamura T, Nakajima H. Activation of CCAAT/enhancer-binding protein alpha or PU.1 in hematopoietic stem cells leads to their reduced self-renewal and proliferation. Stem Cells. 2008;26:3172-81 pubmed publisher..Our data suggest that the activation of C/EBPalpha or PU.1 is sufficient to repress stem cell capacities in HSCs, and their fine-tuned regulation is critical for HSC homeostasis. ..
- Lopez R, Garcia Silva S, Moore S, Bereshchenko O, Martinez Cruz A, Ermakova O, et al. C/EBPalpha and beta couple interfollicular keratinocyte proliferation arrest to commitment and terminal differentiation. Nat Cell Biol. 2009;11:1181-90 pubmed publisher..C/EBPs, therefore, couple basal keratinocyte cell cycle exit to commitment to differentiation through E2F repression and DNA binding, respectively, and may act to restrict the epidermal stem cell compartment. ..
- Porse B, Pedersen TA -, Xu X, Lindberg B, Wewer U, Friis Hansen L, et al. E2F repression by C/EBPalpha is required for adipogenesis and granulopoiesis in vivo. Cell. 2001;107:247-58 pubmed
- Hirai H, Zhang P, Dayaram T, Hetherington C, Mizuno S, Imanishi J, et al. C/EBPbeta is required for 'emergency' granulopoiesis. Nat Immunol. 2006;7:732-9 pubmed..C/EBPbeta inhibited proliferation less severely than did C/EBPalpha. These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors...
- Lefterova M, Zhang Y, Steger D, Schupp M, Schug J, Cristancho A, et al. PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev. 2008;22:2941-52 pubmed publisher..Thus, PPARgamma and C/EBP factors cooperatively orchestrate adipocyte biology by adjacent binding on an unanticipated scale. ..
- Begay V, Smink J, Leutz A. Essential requirement of CCAAT/enhancer binding proteins in embryogenesis. Mol Cell Biol. 2004;24:9744-51 pubmed..Our data thus reveal novel essential, redundant, and dosage dependent functions of C/EBPs. ..
- Rosen E, Hsu C, Wang X, Sakai S, Freeman M, Gonzalez F, et al. C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev. 2002;16:22-6 pubmed..These results indicate that C/EBPalpha and PPARgamma participate in a single pathway of fat cell development with PPARgamma being the proximal effector of adipogenesis. ..
- Wang N, Finegold M, Bradley A, Ou C, Abdelsayed S, Wilde M, et al. Impaired energy homeostasis in C/EBP alpha knockout mice. Science. 1995;269:1108-12 pubmed..This study demonstrates that C/EBP alpha is critical for the establishment and maintenance of energy homeostasis in neonates. ..
- Chen S, Chen J, Johnson P, Muppala V, Lee Y. C/EBPbeta, when expressed from the C/ebpalpha gene locus, can functionally replace C/EBPalpha in liver but not in adipose tissue. Mol Cell Biol. 2000;20:7292-9 pubmed..Moreover, our studies with the C/ebpalpha(beta/beta) mice provide new insights into the nonredundant functions of C/EBPalpha and C/EBPbeta on gene regulation in WAT. ..
- Kirstetter P, Schuster M, Bereshchenko O, Moore S, Dvinge H, Kurz E, et al. Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. Cancer Cell. 2008;13:299-310 pubmed publisherMutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance...
- Wang G, Timchenko N. Dephosphorylated C/EBPalpha accelerates cell proliferation through sequestering retinoblastoma protein. Mol Cell Biol. 2005;25:1325-38 pubmed..Our data demonstrate a new pathway by which the phosphorylation-dependent switch of biological functions of C/EBPalpha promotes liver proliferation. ..
- Tong Q, Tsai J, Tan G, Dalgin G, Hotamisligil G. Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation. Mol Cell Biol. 2005;25:706-15 pubmed
- Chen P, Riley D, Chen Y, Lee W. Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs. Genes Dev. 1996;10:2794-804 pubmed..Such a role contrasts with the function of Rb in arresting cell cycle progression in G1 by negative regulation of other transcription factors like E2F-1. ..
- Westmacott A, Burke Z, Oliver G, Slack J, Tosh D. C/EBPalpha and C/EBPbeta are markers of early liver development. Int J Dev Biol. 2006;50:653-7 pubmed..Both are complementary to the early expression of Pdx1, a key pancreatic transcription factor. These results are consistent with the idea that C/EBP factors are master regulators for liver development. ..
- Hasemann M, Schuster M, Frank A, Theilgaard Monch K, Pedersen T, Nerlov C, et al. Phosphorylation of serine 248 of C/EBP? is dispensable for myelopoiesis but its disruption leads to a low penetrant myeloid disorder with long latency. PLoS ONE. 2012;7:e38841 pubmed publisher..genetics to investigate the significance of C/EBP? serine 248 in vivo through the construction and analysis of Cebpa(S248A/S248A) knock-in mice...
- Loomis K, Zhu S, Yoon K, Johnson P, Smart R. Genetic ablation of CCAAT/enhancer binding protein alpha in epidermis reveals its role in suppression of epithelial tumorigenesis. Cancer Res. 2007;67:6768-76 pubmed..Our study shows that C/EBPalpha is dispensable for epidermal homeostasis and provides genetic evidence that C/EBPalpha is a suppressor of epithelial tumorigenesis. ..
- Wang G, Salisbury E, Shi X, Timchenko L, Medrano E, Timchenko N. HDAC1 cooperates with C/EBPalpha in the inhibition of liver proliferation in old mice. J Biol Chem. 2008;283:26169-78 pubmed publisher..Thus, our data demonstrate that translational elevation of HDAC1 in livers of old mice is involved in the assembly of high M(r) protein-protein complexes that inhibit liver proliferation. ..
- Zhang P, Iwasaki Arai J, Iwasaki H, Fenyus M, Dayaram T, Owens B, et al. Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha. Immunity. 2004;21:853-63 pubmed..Therefore, C/EBP alpha is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity. ..
- Wang G, Shi X, Salisbury E, Timchenko N. Regulation of apoptotic and growth inhibitory activities of C/EBPalpha in different cell lines. Exp Cell Res. 2008;314:1626-39 pubmed publisher..These data show that apoptotic and growth inhibitory activities of C/EBPalpha are differentially regulated in different cells and that cooperation of cyclin D3 and C/EBPalpha is required for the inhibition of proliferation. ..
- Freytag S, Paielli D, Gilbert J. Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells. Genes Dev. 1994;8:1654-63 pubmed..The results demonstrate that C/EBP alpha can efficiently promote the adipogenic program in a variety of mouse fibroblastic cells, including those that have little or no spontaneous capacity to undergo adipogenesis. ..
- Schuster M, Frank A, Bagger F, Rapin N, Vikesaa J, Porse B. Lack of the p42 form of C/EBP? leads to spontaneous immortalization and lineage infidelity of committed myeloid progenitors. Exp Hematol. 2013;41:882-893.e16 pubmed publisher..In this study, we use premalignant cells from a Cebpa mutant AML model, in which the LIC population resembles granulocyte-macrophage progenitors (GMPs), to show that ..
- Seagroves T, Krnacik S, Raught B, Gay J, Burgess Beusse B, Darlington G, et al. C/EBPbeta, but not C/EBPalpha, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland. Genes Dev. 1998;12:1917-28 pubmed..These results demonstrate that C/EBPbeta, but not C/EBPalpha, is required for ductal morphogenesis, lobuloalveolar development, and functional differentiation of mammary epithelial cells. ..
- Wu Z, Rosen E, Brun R, Hauser S, Adelmant G, Troy A, et al. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell. 1999;3:151-8 pubmed..These results define multiple roles for C/EBP alpha in adipogenesis and show that cross-regulation between PPAR gamma and C/EBP alpha is a key component of the transcriptional control of this cell lineage. ..
- Paquin A, Barnabe Heider F, Kageyama R, Miller F. CCAAT/enhancer-binding protein phosphorylation biases cortical precursors to generate neurons rather than astrocytes in vivo. J Neurosci. 2005;25:10747-58 pubmed..Thus, activation of an MEK-C/EBP pathway in cortical precursors in vivo biases them to become neurons and against becoming astrocytes, thereby acting as a growth factor-regulated switch. ..
- di Tullio A, Vu Manh T, Schubert A, Castellano G, Mansson R, Graf T. CCAAT/enhancer binding protein alpha (C/EBP(alpha))-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation. Proc Natl Acad Sci U S A. 2011;108:17016-21 pubmed publisher..Together, our findings are consistent with the notion that the conversion from pre-B cells to macrophages is mostly direct and does not involve overt retrodifferentiation. ..
- Yeh W, Cao Z, Classon M, McKnight S. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev. 1995;9:168-81 pubmed
- Sato A, Xu Y, Whitsett J, Ikegami M. CCAAT/enhancer binding protein-? regulates the protease/antiprotease balance required for bronchiolar epithelium regeneration. Am J Respir Cell Mol Biol. 2012;47:454-63 pubmed publisher..Transgenic Cebp?(?/?) mice, in which Cebpa was conditionally deleted from Clara cells and Type II cells after birth, were used in this study...
- Lee Y, Sauer B, Johnson P, Gonzalez F. Disruption of the c/ebp alpha gene in adult mouse liver. Mol Cell Biol. 1997;17:6014-22 pubmed..These results establish C/EBP alpha as an essential transcriptional regulator of genes encoding enzymes involved in bilirubin detoxification and gluconeogenesis in adult mouse liver. ..
- Tang Q, Zhang J, Daniel Lane M. Sequential gene promoter interactions of C/EBPbeta, C/EBPalpha, and PPARgamma during adipogenesis. Biochem Biophys Res Commun. 2004;319:235-9 pubmed..g., 422/aP2) in the terminally differentiated state. Together these findings provide compelling evidence that C/EBPbeta, C/EBPalpha, and PPARgamma participate in a cascade during adipogenesis. ..
- Timchenko N, Wilde M, Darlington G. C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice. Mol Cell Biol. 1999;19:2936-45 pubmed..The disruption of E2F-p107 complexes correlates with C/EBPalpha-mediated growth arrest of hepatocytes in newborn animals. ..
- Keeshan K, Santilli G, Corradini F, Perrotti D, Calabretta B. Transcription activation function of C/EBPalpha is required for induction of granulocytic differentiation. Blood. 2003;102:1267-75 pubmed
- Keeshan K, He Y, Wouters B, Shestova O, Xu L, Sai H, et al. Tribbles homolog 2 inactivates C/EBPalpha and causes acute myelogenous leukemia. Cancer Cell. 2006;10:401-11 pubmed..Furthermore, Trib2 expression was elevated in a subset of human AML patient samples. Together, our data identify Trib2 as an oncogene that induces AML through a mechanism involving inactivation of C/EBPalpha. ..
- Berg T, Didon L, Nord M. Ectopic expression of C/EBPalpha in the lung epithelium disrupts late lung development. Am J Physiol Lung Cell Mol Physiol. 2006;291:L683-93 pubmed..When this phenotype was compared with that of mice carrying a targeted mutation of the Cebpa gene, the Cebpa-/- mice exhibited a similar developmental phenotype...