Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells.
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.
Bond
Heather M
HM
Department of Experimental and Clinical Medicine Gaetano Salvatore, University of Catanzaro Magna, Graecia, Italy.
Mesuraca
Maria
M
Carbone
Ennio
E
Bonelli
Patrizia
P
Agosti
Valter
V
Amodio
Nicola
N
De Rosa
Gennaro
G
Di Nicola
Massimo
M
Gianni
Alessandro M
AM
Moore
Malcolm A S
MA
Hata
Akiko
A
Grieco
Michele
M
Morrone
Giovanni
G
Venuta
Salvatore
S
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*
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