title: Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells.
abstract: 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.
authors: Department of Experimental and Clinical Medicine Gaetano Salvatore, University of Catanzaro Magna, Graecia, Italy.
authors: Heather M
authors: HM
authors: Bond
authors: Maria
authors: M
authors: Mesuraca
authors: Ennio
authors: E
authors: Carbone
authors: Patrizia
authors: P
authors: Bonelli
authors: Valter
authors: V
authors: Agosti
authors: Nicola
authors: N
authors: Amodio
authors: Gennaro
authors: G
authors: De Rosa
authors: Massimo
authors: M
authors: Di Nicola
authors: Alessandro M
authors: AM
authors: Gianni
authors: Malcolm A S
authors: MA
authors: Moore
authors: Akiko
authors: A
authors: Hata
authors: Michele
authors: M
authors: Grieco
authors: Giovanni
authors: G
authors: Morrone
authors: Salvatore
authors: S
authors: Venuta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D018922:HL-60 Cells; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger; D017386:Sequence Homology, Amino Acid; D051785:Smad Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D020298:U937 Cells; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C081976:EBF1 protein, human; C489921:Ebf1 protein, mouse; C472572:Evi3 protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051785:Smad Proteins; D015534:Trans-Activators; D014157:Transcription Factors