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Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells.

Blood | Mar 15, 2004

http://www.ncbi.nlm.nih.gov/pubmed/14630787

Comparison of the gene expression repertoire in human hematopoietic progenitors and mature leukocytes led to identification of a transcript expressed in CD34+cells and undetectable in differentiated cells. Sequencing of the cDNA (termed EHZF: early hematopoietic zinc finger) revealed 30 zinc fingers with 96% homology to mouse Evi3, a recently identified gene associated with the retroviral integration site in AKXD-27 B-cell lymphomas. EHZF and Evi3 share high homology with the transcription cofactor OAZ, implicated in the control of olfactory epithelium and B-lymphocyte differentiation and in the bone morphogenic protein (BMP) signal transduction. Here we show that (1) EHZF expression is abundant in human CD34+ progenitors and declines rapidly during cytokine-driven differentiation; (2) significant mRNA levels are found in most acute myelogenous leukemias; (3) in response to BMPs EHZF complexes SMADs 1 and 4, binds to, and enhances the transcriptional activity of, a BMP2/4 responsive element; (4) EHZF inhibits the transcriptional activity of early B-cell factor (EBF), a transcription factor essential for specification of the B-cell lineage. Taken together, our data suggest that EHZF is likely to play a relevant role in the control of human hematopoiesis and might be implicated in the development of hematopoietic malignancies.

Pubmed ID: 14630787 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Bone Morphogenetic Proteins | Caco-2 Cells | Carrier Proteins | Cloning, Molecular | DNA-Binding Proteins | Gene Expression | HL-60 Cells | HeLa Cells | Hematopoietic Stem Cells | Humans | Jurkat Cells | Mice | Molecular Sequence Data | Nuclear Proteins | RNA, Messenger | Sequence Homology, Amino Acid | Smad Proteins | Trans-Activators | Transcription Factors | Transcription, Genetic | U937 Cells | Zinc Fingers

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Associated grants

  • Agency: NCI NIH HHS, Id: P01 CA 59350
  • Agency: NHLBI NIH HHS, Id: R01 HL 61401

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