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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-9-27
pubmed:abstractText
In the search for genes expressed in hematopoietic stem cells, we identified that the expression of Gfi-1B (growth factor independence-1B) is highly restricted to hematopoietic stem cells, erythroblasts, and megakaryocytes. Gfi-1 and Gfi-1B are zinc finger proteins that share highly conserved SNAG and 6 zinc finger domains. Gfi-1 has been characterized as an oncogene involved in lymphoid malignancies in mice. In contrast, role of Gfi-1B in hematopoiesis has not been well characterized. In this study, we analyzed its function in human hematopoiesis. Enforced expression of Gfi-1B in human CD34(+) hematopoietic progenitors induced a drastic expansion of erythroblasts in an erythropoietin-independent manner. Expression of Gfi-1B did not promote erythroid commitment, but enhanced proliferation of immature erythroblasts. Erythroblasts expanded by exogenous Gfi-1B, however, failed to differentiate beyond proerythroblast stage and showed massive apoptosis. These biologic effects of Gfi-1B were mediated through its zinc finger domain, but not by the SNAG or non-zinc finger domain. Proliferation of erythroblasts was associated with sustained expression of GATA-2 but not of GATA-1, indicating a potential link between Gfi-1B and GATA family regulators. Importantly, the function of Gfi-1B to modulate transcription was dependent on promoter context. In addition, activation of transcription of an artificial promoter was mediated through its zinc finger domain. These findings establish Gfi-1B as a novel erythroid regulator and reveal its specific involvement in the regulation of erythroid cell growth through modulating erythroid-specific gene expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2769-77
pubmed:dateRevised
2004-11-18
pubmed:meshHeading
pubmed-meshheading:12351384-Animals, pubmed-meshheading:12351384-Base Sequence, pubmed-meshheading:12351384-Cell Culture Techniques, pubmed-meshheading:12351384-Cells, Cultured, pubmed-meshheading:12351384-Colony-Forming Units Assay, pubmed-meshheading:12351384-Conserved Sequence, pubmed-meshheading:12351384-DNA Primers, pubmed-meshheading:12351384-Erythroblasts, pubmed-meshheading:12351384-Erythropoiesis, pubmed-meshheading:12351384-Flow Cytometry, pubmed-meshheading:12351384-Gene Expression Regulation, pubmed-meshheading:12351384-Hematopoiesis, pubmed-meshheading:12351384-Hematopoietic Stem Cells, pubmed-meshheading:12351384-Humans, pubmed-meshheading:12351384-Megakaryocytes, pubmed-meshheading:12351384-Mice, pubmed-meshheading:12351384-Proto-Oncogene Proteins, pubmed-meshheading:12351384-Repressor Proteins, pubmed-meshheading:12351384-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12351384-Zinc Fingers
pubmed:year
2002
pubmed:articleTitle
Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis.
pubmed:affiliation
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and Core Research for Evolutional Science and Technology of Japan Science and Technology, Japan.
pubmed:publicationType
Journal Article