Affinage

CEBPA

CCAAT/enhancer-binding protein alpha · UniProt P49715

Length
358 aa
Mass
37.6 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEBPA encodes a bZIP transcription factor that binds CCAAT/enhancer DNA sequences and serves as a master regulator of myeloid differentiation, adipogenesis, and hepatic metabolism. CEBPA activates lineage-specific gene programs in cooperation with PPARγ in adipocytes and PU.1 in myeloid cells, maintains hematopoietic stem cell quiescence through repression of N-Myc, and inhibits cell-cycle progression via phosphorylation-dependent interactions with CDK2 and E2F-Rb complexes (PMID:18981473, PMID:23502316, PMID:15107404). Its activity is modulated by post-translational phosphorylation—ERK1/2-mediated phosphorylation at Ser21 inhibits granulocytic differentiation while PKC-mediated phosphorylation at Ser248 enhances it—and by direct physical inhibition of the DNMT3A methyltransferase, linking CEBPA to epigenetic regulation (PMID:16446383, PMID:11978795, PMID:35080973). Loss-of-function and N-terminal truncating CEBPA mutations drive acute myeloid leukemia by causing aberrant enhancer activation through recruitment of the MLL1 complex, differentiation block, and DNA hypermethylation at PRC2 target genes (PMID:30679799, PMID:31784538, PMID:35080973).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1988 High

    The initial question of what protein recognizes both CCAAT and enhancer core sequences was resolved by showing a single gene product (C/EBP) accounts for both activities, with a compact 14-kD DNA-binding domain bearing homology to myc/fos oncogenes, establishing CEBPA as a sequence-specific transcription factor.

    Evidence Recombinant protein expression, in vitro DNA-binding assay, and protease domain mapping

    PMID:2850264

    Open questions at the time
    • No in vivo target gene identification
    • Dimerization partners not characterized
    • No physiological function established
  2. 1995 High

    The physiological necessity of CEBPA was established by showing knockout mice die neonatally from hypoglycemia due to failed hepatic glycogen storage, gluconeogenic enzyme induction, and adipocyte lipid accumulation, defining CEBPA as essential for metabolic gene programs.

    Evidence Targeted gene deletion in mice with metabolic and gene expression phenotyping

    PMID:7652557

    Open questions at the time
    • Hematopoietic role not yet addressed in KO
    • Direct vs. indirect transcriptional targets not distinguished
  3. 1998 High

    Beyond metabolism, CEBPA was shown to be sufficient to induce myeloid and eosinophil lineage commitment in multipotent progenitors, with transactivation-independent functions required for lineage specification and transactivation-dependent functions for maturation, revealing separable differentiation mechanisms.

    Evidence Forced expression of wild-type and transactivation-deficient alleles in multipotent progenitors with differentiation assays

    PMID:9694805

    Open questions at the time
    • In vivo hematopoietic requirement not yet shown
    • Downstream differentiation targets unknown
  4. 2002 High

    How signaling pathways tune CEBPA activity was answered by identifying two opposing phosphorylation events: Ras/PKC-mediated Ser248 phosphorylation enhances granulocytic differentiation, while FLT3/ERK1/2-mediated Ser21 phosphorylation inhibits it, establishing post-translational control as a regulatory axis exploited in AML.

    Evidence Site-directed mutagenesis (S248A, S21A, S21D), in vivo phosphorylation assays, PKC/MEK inhibitors, granulocytic differentiation assays in MV4;11 cells

    PMID:11978795 PMID:16446383

    Open questions at the time
    • Full phosphoproteome of CEBPA not mapped
    • Kinase-substrate interaction structures not resolved
  5. 2004 High

    The mechanism by which CEBPA arrests cell growth was clarified: phosphorylation at Ser193 is required for physical interaction with CDK2 and E2F-Rb complexes, and PI3K/Akt-driven PP2A dephosphorylation at this site abolishes growth arrest, connecting metabolic signaling to cell-cycle control.

    Evidence S193A mutagenesis, co-immunoprecipitation with CDK2 and E2F-Rb, PI3K/Akt and PP2A pharmacological inhibition in liver tumor cells

    PMID:15107404

    Open questions at the time
    • Structural basis of CDK2/E2F interaction not resolved
    • Relative contribution of each cell-cycle target unclear
  6. 2008 High

    Genome-wide occupancy analysis revealed that CEBPA co-occupies ~3350 sites with PPARγ in adipocytes, establishing that the two factors cooperatively regulate the adipogenic transcriptional program rather than acting independently.

    Evidence ChIP-chip genome-wide tiling arrays in 3T3-L1 adipocytes

    PMID:18981473

    Open questions at the time
    • Causal hierarchy between CEBPA and PPARγ at co-bound sites not resolved
    • Enhancer vs. promoter function not distinguished
  7. 2013 High

    A key question about how HSCs maintain quiescence was addressed by showing that CEBPA-deficient adult HSCs hyperproliferate due to de-repression of N-Myc, establishing CEBPA as a direct regulator of HSC self-renewal independent of its differentiation function.

    Evidence Inducible Cebpa knockout mouse with transcriptional profiling and functional HSC assays

    PMID:23502316

    Open questions at the time
    • Whether CEBPA directly binds N-Myc regulatory regions not confirmed by ChIP
    • Interaction with other quiescence regulators not explored
  8. 2016 High

    The cis-regulatory architecture controlling tissue-specific CEBPA expression was defined by showing a single +42 kb enhancer is essential exclusively for hematopoietic CEBPA expression; its deletion causes granulocytic failure and HSC loss without affecting non-hematopoietic organs.

    Evidence CRISPR/Cas9 enhancer deletion in mice with sorted progenitor gene expression profiling

    PMID:26966090

    Open questions at the time
    • Trans-acting factors at this enhancer beyond RUNX1 not fully defined
    • Whether additional enhancers exist for fine-tuning within hematopoiesis
  9. 2019 High

    How N-terminal CEBPA mutations cause leukemia was mechanistically explained: the truncated p30 isoform recruits the MLL1 histone-methyltransferase complex to aberrant enhancers, directly activating GATA2 and the CD73/A2AR pathway to sustain leukemic growth and block differentiation.

    Evidence Reciprocal co-immunoprecipitation, ChIP-seq for p30 and MLL1, CRISPR MLL1 knockout, cross-species ChIP-seq, in vivo CD73 pathway inhibition

    PMID:30679799 PMID:31309149

    Open questions at the time
    • How p30 gains MLL1 interaction absent in full-length CEBPA not structurally resolved
    • Complete set of aberrant p30 target enhancers not cataloged
  10. 2022 High

    A non-transcriptional function of CEBPA was uncovered: it directly binds the long DNMT3A isoform and physically blocks its access to DNA substrate, inhibiting methyltransferase activity; AML-associated C-terminal CEBPA mutations (e.g., N321D) disrupt this interaction, causing DNA hypermethylation at PRC2 targets.

    Evidence Co-immunoprecipitation, in vitro reconstituted methyltransferase inhibition assay, bisulfite methylation profiling of CEBPA-mutant leukemia

    PMID:35080973

    Open questions at the time
    • Structural basis of CEBPA-DNMT3A interface not determined
    • Whether this mechanism operates in non-hematopoietic tissues unknown
  11. 2023 Medium

    CEBPA's intrinsically disordered region was shown to undergo phase separation in vitro and form nuclear foci that promote long-range 3D chromatin hubs during transdifferentiation, suggesting phase separation as a mechanism for CEBPA's pioneer-like genome reorganization activity.

    Evidence In vitro phase separation assay with IDR mutagenesis, live-cell imaging, Hi-C/chromatin conformation capture during B-to-macrophage transdifferentiation

    PMID:37516962

    Open questions at the time
    • Causal link between phase separation and transcriptional output not established in vivo
    • Whether phase separation is required for normal hematopoiesis untested
    • IDR mutants not tested in differentiation functional assays
  12. 2024 High

    CEBPA's role was extended beyond hematopoiesis: in alveolar type 2 cells, CEBPA recruits the lung lineage factor NKX2-1 to maintain the AT2 program and restrict plasticity; without CEBPA, cells reactivate the SOX9 progenitor program and aberrantly generate transitional cell states after injury.

    Evidence Conditional Cebpa knockout in AT2 cells, ChIP/co-IP for CEBPA-NKX2-1 interaction, ATAC-seq, Sendai virus injury model

    PMID:38755149

    Open questions at the time
    • Whether CEBPA-NKX2-1 interaction is direct or within a complex not resolved
    • Relevance to lung fibrosis or adenocarcinoma progression not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CEBPA interactions with DNMT3A and MLL1, whether phase separation is functionally required for CEBPA's transcriptional and pioneer activities in vivo, the full spectrum of CEBPA's non-transcriptional functions, and how CEBPA integrates multiple post-translational modifications to coordinate differentiation versus quiescence decisions.
  • No high-resolution structure of CEBPA-DNMT3A or CEBPA-MLL1 complex
  • In vivo functional requirement for phase separation untested
  • Combinatorial phosphorylation code not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 5 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2
Partners
CDK2CEBPBDNMT3AMLL1NKX2-1PPARGRUNX1SPI1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 C/EBP (CEBPA) binds both the CCAAT homology and enhancer core homology sequences; a single gene product accounts for both binding activities, with a 14-kD DNA-binding domain identified by protease mapping, and a 60-amino-acid segment within this domain bears sequence similarity to myc and fos oncogenes. Bacterial expression of recombinant clone, in vitro DNA-binding assay, protease fragment analysis, sequence analysis Genes & development High 2850264
1991 C/EBP alpha (CEBPA) protein is expressed in the late phase of adipocyte differentiation in 3T3-L1 cells, downstream of C/EBP beta and C/EBP delta, consistent with a regulatory cascade controlling terminal adipocyte differentiation; C/EBP beta and delta form heterodimers with C/EBP alpha and activate transcription from the serum albumin promoter. Western/Northern blotting during 3T3-L1 differentiation, transient transfection reporter assays, heterodimerization assay Genes & development High 1840554
1991 C/EBP alpha (CEBPA) binds to and transactivates enhancer element II of hepatitis B virus in liver cells. EMSA (gel shift), transient cotransfection reporter assay Virology Medium 1853580
1995 C/EBP alpha (CEBPA) is required for hepatic glycogen storage, transcriptional induction of gluconeogenic enzymes (PEPCK and glucose-6-phosphatase), and lipid accumulation in hepatocytes and adipocytes; knockout mice die from neonatal hypoglycemia. Targeted gene deletion (knockout mouse), gene expression analysis, biochemical assays Science High 7652557
1998 C/EBP alpha binds to and transactivates the leptin gene promoter through a C/EBP binding motif; mutation of this motif reduces promoter activity approximately 10-fold and abolishes C/EBP alpha binding. Mutational analysis of promoter, EMSA, transient transfection reporter assay Endocrinology Medium 9492033
1998 C/EBP alpha (and C/EBP beta) induces both myeloid and eosinophil lineage commitment in multipotent hematopoietic progenitors; transactivation-independent C/EBP functions are required for eosinophil lineage commitment while transactivation-dependent functions are required for maturation. Forced expression of wild-type and transactivation-deficient C/EBP alleles in transformed multipotent progenitors (MEPs), conditional C/EBP allele activation, differentiation assays Genes & development High 9694805
2002 Ras signaling enhances C/EBP alpha transcriptional activity to induce granulocytic differentiation by phosphorylation of serine 248 via a PKC-dependent pathway; S248A mutation abolishes both Ras-mediated transactivation enhancement and C/EBP alpha-induced granulocytic differentiation. Gal4-fusion transactivation assay, site-directed mutagenesis (S248A), in vivo phosphorylation assay, PKC inhibitor treatment, differentiation assay The Journal of biological chemistry High 11978795
2003 Dominant-negative C/EBP (A-C/EBP) forms stable inactive heterodimers with C/EBP beta in vitro and blocks mitotic clonal expansion during adipogenesis by preventing nuclear import of C/EBP beta, thereby inhibiting expression of C/EBP alpha and PPARgamma downstream. Adenoviral A-C/EBP expression in 3T3-L1 cells, immunofluorescence staining, DNA replication assays, flow cytometry for cell cycle Proceedings of the National Academy of Sciences of the United States of America High 14688407
2004 PI3K/Akt pathway activation in liver tumor cells causes PP2A-mediated dephosphorylation of C/EBP alpha at Ser193, blocking its growth inhibitory activity; mutation of Ser193 to Ala abolishes C/EBP alpha interaction with cdk2 and E2F-Rb complexes and prevents growth arrest. Site-directed mutagenesis (S193A), co-immunoprecipitation with cdk2 and E2F-Rb, growth arrest assay, pharmacological inhibition of PI3K/Akt and PP2A Genes & development High 15107404
2006 FLT3-activating mutations in AML inhibit C/EBP alpha function through ERK1/2-mediated phosphorylation at serine 21; the S21A mutation restores granulocytic differentiation, while the phosphomimetic S21D mutation does not, demonstrating this is the relevant phosphorylation site. Site-directed mutagenesis (S21A, S21D), stable expression in MV4;11 cells, pharmacological inhibition of FLT3/MEK, granulocytic differentiation assay The Journal of experimental medicine High 16446383
2008 C/EBP alpha genome-wide co-occupies approximately 3350 genomic regions together with PPARgamma in adipocytes; most adipogenesis-induced genes are bound by both factors, and both C/EBP alpha and beta are required along with PPARgamma for robust adipocyte-specific gene expression. ChIP-chip (ChIP coupled to genome-wide tiling arrays), ChIP in 3T3-L1 adipocytes Genes & development High 18981473
2009 Calreticulin, induced by UPR/ER stress via the ATF6 pathway, binds to CEBPA mRNA and blocks its translation, suppressing C/EBP alpha protein expression and myeloid differentiation in AML. Conditional calreticulin expression in U937 cells, mRNA-protein interaction assay (calreticulin-CEBPA mRNA binding), reporter analysis of calreticulin promoter ERSE elements, patient sample analysis Journal of cellular and molecular medicine Medium 19659458
2010 C/EBP alpha directly regulates miR-34a expression during granulopoiesis; miR-34a targets E2F3 to block myeloid cell proliferation; AML samples with CEBPA mutations show reduced miR-34a and elevated E2F3 and E2F1. Reporter assay, ChIP, manipulation of miR-34a in AML blast cells, patient sample gene expression analysis Blood Medium 20889924
2012 RUNX1 directly binds the CEBPA promoter and a conserved +37 kb enhancer region (with 4 Runx1 binding sites); RUNX1 loss reduces Cebpa mRNA in myeloid progenitors; exogenous C/EBP alpha rescues granulopoiesis in Runx1-deleted marrow, establishing RUNX1 as a direct upstream regulator of CEBPA. ChIP, enhancer mutagenesis in reporter assay, RUNX1-ER inducible system with cycloheximide, Runx1 knockout mice, exogenous C/EBP alpha rescue Blood High 22451420
2013 C/EBP alpha controls adult HSC quiescence; C/EBP alpha-deficient adult HSCs show increased proliferation and number; N-Myc is identified as a downstream target of C/EBP alpha, and C/EBP alpha loss causes de-repression of N-Myc. Inducible Cebpa knockout mouse, transcriptional profiling, functional HSC assays Nature cell biology High 23502316
2015 p53 and KLF4 directly activate CEBPA gene transcription; in AML, p53 inactivation (correlated with elevated XPO1/CRM1, MDM2, CUL9/PARC) leads to reduced KLF4 and CEBPA protein levels; restoring p53 function induces CEBPA expression and myeloid differentiation. Reporter assays, protein level analysis in AML patient samples, pharmacological p53 restoration, differentiation assay Clinical cancer research Medium 26408402
2016 A single enhancer at +42 kb from CEBPA is essential for CEBPA expression exclusively in hematopoietic stem cells and myeloid-primed progenitors; germline deletion of this enhancer in mice causes severe granulocytic defects and loss of HSC maintenance without affecting CEBPA expression in other organs. CRISPR/Cas9 enhancer deletion in mice (in vivo), chromatin topology analysis, gene expression profiling in sorted progenitors Blood High 26966090
2017 R-2HG inhibits FTO demethylase activity, increasing global m6A RNA modification, which decreases the stability of CEBPA (and MYC) transcripts in sensitive leukemia cells, suppressing relevant signaling pathways. FTO activity assay, m6A RNA sequencing, mRNA stability assay, ectopic IDH1 mutation expression, FTO overexpression/knockdown Cell High 29249359
2017 Small activating RNA (saRNA) targeting the CEBPA gene locus increases CEBPA transcription in a sequence-specific manner requiring Argonaute-2 (Ago2); the guide strand associates with Ago2 and localizes to the CEBPA genomic locus. Nuclear run-on assay, RNA ChIP (Ago2 association with CEBPA locus), saRNA gain-of-function in hepatocellular carcinoma cells Molecular therapy Medium 28882451
2019 Oncogenic C/EBP alpha p30 isoform (from N-terminal CEBPA mutations) physically interacts with the MLL1 histone-methyltransferase complex and co-localizes with MLL1 genome-wide; MLL1 complex loss causes differentiation arrest reversal in C/EBP alpha p30-expressing cells; GATA2 is identified as a direct critical target of the p30-MLL1 interaction. Co-immunoprecipitation (p30-MLL1 interaction), ChIP-seq (genome-wide co-localization), CRISPR/Cas9 MLL1 mutagenesis, pharmacological MLL1 complex inhibition, differentiation assays Leukemia High 30679799
2019 The leukemia-associated CEBPA-p30 isoform occupies aberrantly activated enhancers and directly drives Nt5e/CD73 expression; CD73 sustains leukemic growth via the CD73/A2AR axis; targeting this pathway enhances survival of AML-transplanted mice. Microscale in vivo ChIP-seq, cross-species gene expression analysis (human AML and Cebpa Lp30 mouse model), functional CD73/A2AR pathway inhibition in vivo Science advances High 31309149
2019 Activating CSF3R mutations cooperate with loss-of-function CEBPA mutations to promote acute leukemia; mutant CEBPA prevents activation of a subset of myeloid lineage enhancers required for differentiation; CEBPA mutation must occur as the initial event in AML initiation. Mouse leukemia model with defined mutation order, chromatin/enhancer analysis, epistasis experiments Nature communications Medium 31784538
2021 Chronic IL-1β exposure selects for Cebpa-knockout hematopoietic progenitors because C/EBP alpha normally mediates IL-1β-induced differentiation and stem cell gene expression repression; Cebpa-KO HSPCs are resistant to these prodifferentiative effects and competitively expand; ectopic CEBPA reduces fitness of established human AML coinciding with increased differentiation. Competitive transplantation of Cebpa-KO vs wild-type HSPCs with chronic IL-1β treatment, gene expression profiling, ectopic CEBPA expression in human AML The Journal of experimental medicine High 33914855
2022 CEBPA protein directly interacts with the long isoform DNMT3A (but not DNMT3A2) and blocks DNMT3A from accessing DNA substrate, thereby inhibiting its methyltransferase activity; tumor-associated CEBPA mutations (e.g., N321D) disrupt DNMT3A association and cause aberrant DNA hypermethylation at PRC2 target genes. Co-immunoprecipitation (CEBPA-DNMT3A interaction), in vitro methyltransferase activity assay with CEBPA blocking, bisulfite/methylation profiling of CEBPA mutant leukemia, mutagenesis of CEBPA interaction domain Science advances High 35080973
2023 The intrinsically disordered region (IDR) of CEBPA undergoes phase separation in vitro dependent on aromatic residues; CEBPA forms nuclear foci and promotes long-range 3D chromatin hubs at CEBPA-bound regions during B cell-to-macrophage transdifferentiation; phase separation may underlie foci formation and 3D genome organization. In vitro phase separation assay with IDR mutagenesis, live-cell imaging of CEBPA foci, Hi-C/chromatin conformation analysis (ChIP-seq, ATAC-seq), transdifferentiation model Cell reports Medium 37516962
2024 CEBPA restricts alveolar type 2 (AT2) cell plasticity by promoting the AT2 transcriptional program and recruiting the lung lineage transcription factor NKX2-1; without CEBPA, neonatal AT2 cells reactivate the SOX9 progenitor program, and after Sendai virus injury mature AT2 cells also aberrantly express SOX9 and more readily form KRT8/CLDN4+ transitional cells. Conditional Cebpa knockout in AT2 cells, ChIP/co-immunoprecipitation for CEBPA-NKX2-1 interaction, ATAC-seq (epigenetic maturation), viral injury model, immunofluorescence Nature communications High 38755149
2003 C/EBP alpha binds two regions of the bcl-2 P2 promoter and increases bcl-2 expression in t(14;18) lymphoma cells; siRNA-mediated knockdown of C/EBP alpha reduces Bcl-2 protein levels; in vivo binding confirmed by ChIP. Reporter assay, EMSA, ChIP, siRNA knockdown, Western blot Oncogene Medium 12970736
2018 CEBPA acts as a pioneer factor in THP-1 monocytes, co-occupying approximately one-third of genomic VDR binding sites; CEBPA binding strength is modulated by 1,25(OH)2D3; CEBPA silencing reveals it enhances basal expression and ligand-inducibility of ~70 vitamin D target genes and suppresses ~82 others, with PU.1 occupancy on CEBPA enhancers mechanistically explaining the dichotomy. ChIP-seq (CEBPA cistrome), RNA-seq after CEBPA silencing, ChIP for H3K4me3 and PU.1 Biochimica et biophysica acta. Gene regulatory mechanisms Medium 30550771
2018 STAT3 induces C/EBP alpha/beta expression, which suppresses MITF transcription by binding to the MITF enhancer region; ATAC-seq confirmed CEBPa/b binding to the MITF enhancer leads to silencing of the MITF locus in melanoma cells. STAT3 knockout mouse melanoma model, CEBP knockdown, ATAC-seq, gene expression profiling Oncogene Medium 33323974
2018 C/EBP alpha (CEBPA) controls cystatin F expression by binding to the CST7 gene promoter during monocyte differentiation; upon PMA-induced differentiation to macrophages, C/EBP alpha protein level decreases and its binding to the CST7 promoter is reduced, leading to decreased cystatin F and increased intracellular cysteine cathepsin activity. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation, immunofluorescence confocal microscopy, proximity ligation assay European journal of cell biology Medium 30033148

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes & development 1511 1840554
1988 Isolation of a recombinant copy of the gene encoding C/EBP. Genes & development 926 2850264
2017 R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling. Cell 908 29249359
1995 Impaired energy homeostasis in C/EBP alpha knockout mice. Science (New York, N.Y.) 815 7652557
2008 PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes & development 688 18981473
1994 C/EBP is an immediate-early gene required for the consolidation of long-term facilitation in Aplysia. Cell 474 8137425
1999 A C/EBP beta isoform recruits the SWI/SNF complex to activate myeloid genes. Molecular cell 276 10619021
2005 Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors. Journal of cell science 237 15944395
1995 The C/EBP family of transcription factors. Immunobiology 220 8530141
2012 C/EBP transcription factors mediate epicardial activation during heart development and injury. Science (New York, N.Y.) 188 23160954
2006 Block of C/EBP alpha function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations. The Journal of experimental medicine 172 16446383
2003 Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes. Proceedings of the National Academy of Sciences of the United States of America 157 14688407
2004 Ras induces mediator complex exchange on C/EBP beta. Molecular cell 147 14759369
2001 Altered expression of C/EBP family members results in decreased adipogenesis with aging. American journal of physiology. Regulatory, integrative and comparative physiology 145 11353682
2005 Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia. Blood 127 15985538
2004 Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBP alpha growth inhibitory activity. Genes & development 123 15107404
1998 Regulation of leptin promoter function by Sp1, C/EBP, and a novel factor. Endocrinology 122 9492033
2013 C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence. Nature cell biology 119 23502316
2018 PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior of glioma cells. Theranostics 117 29464001
2022 CEBPA mutations in 4708 patients with acute myeloid leukemia: differential impact of bZIP and TAD mutations on outcome. Blood 114 34320176
2010 C/EBPα regulated microRNA-34a targets E2F3 during granulopoiesis and is down-regulated in AML with CEBPA mutations. Blood 112 20889924
1998 The C/EBP family of transcription factors in the liver and other organs. International journal of experimental pathology 104 10319019
1991 Transcriptional factor C/EBP binds to and transactivates the enhancer element II of the hepatitis B virus. Virology 100 1853580
2017 Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer. Molecular therapy : the journal of the American Society of Gene Therapy 94 28882451
2003 Mutations of CEBPA in acute myeloid leukemia FAB types M1 and M2. Genes, chromosomes & cancer 92 12661007
1998 Distinct C/EBP functions are required for eosinophil lineage commitment and maturation. Genes & development 92 9694805
2009 Complexity of CEBPA dysregulation in human acute myeloid leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 89 19706798
2012 Runx1 deletion or dominant inhibition reduces Cebpa transcription via conserved promoter and distal enhancer sites to favor monopoiesis over granulopoiesis. Blood 86 22451420
2011 IMiD immunomodulatory compounds block C/EBP{beta} translation through eIF4E down-regulation resulting in inhibition of MM. Blood 83 21389327
2005 A transcriptional role for C/EBP beta in the neuronal response to axonal injury. Molecular and cellular neurosciences 79 15936952
2013 C/EBP homologous protein-induced macrophage apoptosis protects mice from steatohepatitis. The Journal of biological chemistry 76 23720735
2018 Gene activation of CEBPA using saRNA: preclinical studies of the first in human saRNA drug candidate for liver cancer. Oncogene 74 29511346
2020 Secondary leukemia in patients with germline transcription factor mutations (RUNX1, GATA2, CEBPA). Blood 71 32430494
2016 An autonomous CEBPA enhancer specific for myeloid-lineage priming and neutrophilic differentiation. Blood 71 26966090
2004 Effect of a C/EBP gene replacement on mitochondrial biogenesis in fat cells. Genes & development 69 15289464
2018 Localized hypoxia links ER stress to lung fibrosis through induction of C/EBP homologous protein. JCI insight 67 30135303
2010 C/EBP{delta} targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression. Proceedings of the National Academy of Sciences of the United States of America 65 20439707
2002 Ras signaling enhances the activity of C/EBP alpha to induce granulocytic differentiation by phosphorylation of serine 248. The Journal of biological chemistry 65 11978795
2013 C/EBP homologous protein drives pro-catabolic responses in chondrocytes. Arthritis research & therapy 62 24351550
2018 Apigetrin inhibits adipogenesis in 3T3-L1 cells by downregulating PPARγ and CEBP-α. Lipids in health and disease 59 29695233
2010 Characterization of CEBPA mutations and promoter hypermethylation in pediatric acute myeloid leukemia. Haematologica 57 21134981
1999 Activation and degradation of the transcription factor C/EBP during long-term facilitation in Aplysia. Journal of neurochemistry 56 10582601
2021 Chronic interleukin-1 exposure triggers selection for Cebpa-knockout multipotent hematopoietic progenitors. The Journal of experimental medicine 52 33914855
2003 Subnuclear localization of C/EBP beta is regulated by growth hormone and dependent on MAPK. The Journal of biological chemistry 51 12821655
1995 Normal fibroblasts induce the C/EBP beta and ATF-4 bZIP transcription factors in response to anoxia. Experimental cell research 51 7664842
2020 STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pathway. Oncogene 49 33323974
2017 Familial CEBPA-mutated acute myeloid leukemia. Seminars in hematology 49 28637622
2017 A Bach2-Cebp Gene Regulatory Network for the Commitment of Multipotent Hematopoietic Progenitors. Cell reports 48 28273455
2003 Transcription cooperation by NFAT.C/EBP composite enhancer complex. The Journal of biological chemistry 48 12606546
2014 MiR-182 is up-regulated and targeting Cebpa in hepatocellular carcinoma. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 47 24653623
2022 LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC. Journal of experimental & clinical cancer research : CR 45 36471363
2011 Stress-induced C/EBP homology protein (CHOP) represses MyoD transcription to delay myoblast differentiation. PloS one 44 22242125
2018 Genetic heterogeneity of cytogenetically normal AML with mutations of CEBPA. Blood advances 43 30337300
2015 Inactivation of the p53-KLF4-CEBPA Axis in Acute Myeloid Leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 43 26408402
2012 Inhibition of CD200R1 expression by C/EBP β in reactive microglial cells. Journal of neuroinflammation 42 22776069
2008 SHARP1/DEC2 inhibits adipogenic differentiation by regulating the activity of C/EBP. EMBO reports 41 19029947
2015 DNA methyltransferase 1 functions through C/ebpa to maintain hematopoietic stem and progenitor cells in zebrafish. Journal of hematology & oncology 40 25886310
2019 Mutant CEBPA directly drives the expression of the targetable tumor-promoting factor CD73 in AML. Science advances 39 31309149
2019 Estradiol stimulates adipogenesis and Slc2a4/GLUT4 expression via ESR1-mediated activation of CEBPA. Molecular and cellular endocrinology 38 31100494
2018 Development of MTL-CEBPA: Small Activating RNA Drug for Hepatocellular Carcinoma. Current pharmaceutical biotechnology 37 29886828
2003 Regulation of Bcl-2 expression by C/EBP in t(14;18) lymphoma cells. Oncogene 37 12970736
2013 Ablation of C/EBP homologous protein does not protect T17M RHO mice from retinal degeneration. PloS one 35 23646198
2022 Acute Myeloid Leukemia With CEBPA Mutations: Current Progress and Future Directions. Frontiers in oncology 34 35178345
2018 Modulation of vitamin D signaling by the pioneer factor CEBPA. Biochimica et biophysica acta. Gene regulatory mechanisms 34 30550771
2015 CEBPA methylation and mutation in myelodysplastic syndrome. Medical oncology (Northwood, London, England) 34 26025484
2019 Anti-inflammatory Activity of MTL-CEBPA, a Small Activating RNA Drug, in LPS-Stimulated Monocytes and Humanized Mice. Molecular therapy : the journal of the American Society of Gene Therapy 33 30852139
2007 C/EBP homologous protein is crucial for the acceleration of experimental pancreatitis. Biochemical and biophysical research communications 33 18166146
2006 C/EBP homologous protein is necessary for normal osteoblastic function. Journal of cellular biochemistry 33 16220546
2014 Mmu-miR-615-3p regulates lipoapoptosis by inhibiting C/EBP homologous protein. PloS one 31 25314137
2010 C/EBP{delta} and STAT-1 are required for TLR8 transcriptional activity. The Journal of biological chemistry 31 20829351
2016 Coordinated inhibition of C/EBP by Tribbles in multiple tissues is essential for Caenorhabditis elegans development. BMC biology 30 27927209
2009 Unfolded protein response suppresses CEBPA by induction of calreticulin in acute myeloid leukaemia. Journal of cellular and molecular medicine 30 19659458
2022 Tumor suppressor CEBPA interacts with and inhibits DNMT3A activity. Science advances 29 35080973
2019 Myeloid lineage enhancers drive oncogene synergy in CEBPA/CSF3R mutant acute myeloid leukemia. Nature communications 29 31784538
2015 Structural Modeling of GR Interactions with the SWI/SNF Chromatin Remodeling Complex and C/EBP. Biophysical journal 28 26278180
2006 FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBP alpha. Oncogene 28 16909111
2019 CEBPA-mutated leukemia is sensitive to genetic and pharmacological targeting of the MLL1 complex. Leukemia 27 30679799
2011 Berberine exerts anti-adipogenic activity through up-regulation of C/EBP inhibitors, CHOP and DEC2. Biochemical and biophysical research communications 27 21893041
2021 METTL3/14 and IL-17 signaling contribute to CEBPA-DT enhanced oral cancer cisplatin resistance. Oral diseases 26 34807506
2019 lncRNA CEBPA-AS1 Overexpression Inhibits Proliferation and Migration and Stimulates Apoptosis of OS Cells via Notch Signaling. Molecular therapy. Nucleic acids 26 32160715
2018 Impaired DNA demethylation of C/EBP sites causes premature aging. Genes & development 26 29884649
2024 CEBPA restricts alveolar type 2 cell plasticity during development and injury-repair. Nature communications 25 38755149
2018 Foxp3 expression in induced regulatory T cells is stabilized by C/EBP in inflammatory environments. EMBO reports 25 30348891
2010 Methylation of TET2, CBL and CEBPA in Ph-negative myeloproliferative neoplasms. Journal of clinical pathology 25 20671051
2019 Gain-of-Function Effects of N-Terminal CEBPA Mutations in Acute Myeloid Leukemia. BioEssays : news and reviews in molecular, cellular and developmental biology 24 31867767
2021 Allele-specific expression of GATA2 due to epigenetic dysregulation in CEBPA double-mutant AML. Blood 23 33831168
2016 Role of C/EBP-α in Adriamycin-induced podocyte injury. Scientific reports 23 27644413
2000 Regulation of Gadd45gamma expression by C/EBP. European journal of biochemistry 23 11012671
2023 CEBPA phase separation links transcriptional activity and 3D chromatin hubs. Cell reports 22 37516962
2019 Shikonin induces apoptosis and suppresses growth in keratinocytes via CEBP-δ upregulation. International immunopharmacology 22 31075711
2019 Companion gene mutations and their clinical significance in AML with double mutant CEBPA. Cancer gene therapy 22 31477806
2019 Targeted regulation of fibroblast state by CRISPR-mediated CEBPA expression. Respiratory research 21 31829168
2018 MiR-486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro. Cancer medicine 21 30073773
2013 Methylation status of CEBPA gene promoter in chronic myeloid leukemia. Hematology (Amsterdam, Netherlands) 21 23541085
1997 C/EBP activates the human corticotropin-releasing hormone gene promoter. Molecular and cellular endocrinology 21 9406848
2008 The HIF-1 alpha-C/EBP alpha axis. Science signaling 20 18957690
2021 MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models. International journal of molecular sciences 19 34502076
2018 The transcription factor C/EBP α controls the role of cystatin F during the differentiation of monocytes to macrophages. European journal of cell biology 19 30033148
2012 Overexpression of wild-type or mutants forms of CEBPA alter normal human hematopoiesis. Leukemia 19 22371011
2012 Asthma and COPD - The C/EBP Connection. The open respiratory medicine journal 17 22715349