Induction of C/EBPα activity alters gene expression and differentiation of human CD34+ cells Journal Article
| Authors: | Cammenga, J.; Mulloy, J. C.; Berguido, F. J.; Macgrogan, D.; Viale, A.; Nimer, S. D. |
| Article Title: | Induction of C/EBPα activity alters gene expression and differentiation of human CD34+ cells |
| Abstract: | The CCAAT/enhancer binding protein alpha (C/EBPα) belongs to a family of transcription factors that are involved in the differentiation process of numerous tissues, including the liver and hematopoietic cells. C/EBPα-/- mice show a block in hematopoietic differentiation, with an accumulation of myeloblasts and an absence of mature granulocytes, whereas expression of C/EBPα in leukemia cell lines leads to granulocytic differentiation. Recently, dominant-negative mutations in the C/EBPα gene and down-regulation of C/EBPα by AML1-ETO, an AML associated fusion protein, have been identified in acute myelogenous leukemia (AML). To better understand the role of C/EBPα in the lineage commitment and differentiation of hematopoietic progenitors, we transduced primary human CD34+ cells with a retroviral construct that expresses the C/EBPα cDNA fused in-frame with the estrogen receptor ligand-binding domain. Induction of C/EBPα function in primary human CD34+ cells, by the addition of β-estradiol, leads to granulocytic differentiation and inhibits erythrocyte differentiation. Using Affymetrix (Santa Clara, CA) oligonucleotide arrays we have identified C/EBPα target genes in primary human hematopoietic cells, including granulocyte-specific genes that are involved in hematopoietic differentiation and inhibitor of differentiation I (Id1), a transcriptional repressor known to interfere with erythrocyte differentiation. Given the known differences in murine and human promoter regulatory sequences, this inducible system allows the identification of transcription factor target genes in a physiologic, human hematopoietic progenitor cell background. © 2003 by The American Society of Hematology. |
| Keywords: | controlled study; protein expression; unclassified drug; acute granulocytic leukemia; gene mutation; gene sequence; human cell; genetics; nonhuman; flow cytometry; protein domain; protein function; mouse; cytology; metabolism; cd34 antigen; reverse transcription polymerase chain reaction; gene expression; gene expression profiling; erythroid precursor cell; inhibitor of differentiation 1; protein protein interaction; transcription factor; cell differentiation; transfection; physiology; cell lineage; genetic transduction; transcription factors; rna; gene expression regulation; blotting, western; fluorescent antibody technique; chemistry; transcription regulation; hybrid protein; neutrophil; genetic transfection; recombinant fusion proteins; reverse transcriptase polymerase chain reaction; oligonucleotide array sequence analysis; gene identification; western blotting; hematopoietic cell; hematopoietic stem cells; protein induction; binding site; neutrophils; down regulation; receptors, estrogen; binding sites; erythrocyte; dna microarray; hematopoietic stem cell; inhibitor of differentiation protein 1; estrogen receptor; estradiol; unindexed sequence; repressor protein; repressor proteins; ligand binding; granulocyte; complementary dna; retrovirus; retroviridae; erythrocytes; leukemia cell line; erythroid progenitor cells; repressor gene; regulator gene; protein aml1 eto; ccaat enhancer binding protein alpha; ccaat-enhancer-binding protein-alpha; myeloblast; humans; human; priority journal; article; id1 protein, human |
| Journal Title: | Blood |
| Volume: | 101 |
| Issue: | 6 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2003-03-15 |
| Start Page: | 2206 |
| End Page: | 2214 |
| Language: | English |
| DOI: | 10.1182/blood-2002-05-1546 |
| PUBMED: | 12406909 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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