Opposing effects of two zinc finger genes, EVI-1 and GATA-1, on all-trans retinoic acid-induced NB4 cell granulocytic differentiation
AdvisorBowden, G. Timothy
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractIn hematopoietic stem cells, lineage specific differentiation is determined in part by specific transcription factors which stabilize a particular lineage network and activate differentiation programs. In myeloid and erythroid lineages, distinct transcription factors are expressed in committed progenitors and more differentiated cells. Zinc finger transcription factors, EVI-1 and GATA-1, are expressed in hematopoietic stem cells. Abnormal EVI-1 expression is associated with some human acute myeloid leukemias (AML). It has been shown that enforced EVI-1 expression blocked erythroid specific transcription factor, GATA-1, mediated transcriptional activation and erythroid differentiation. The regulation and the function of the EVI-1 in myeloid differentiation and possible antagonism of erythroid/myeloid lineage transcription factors in lineage commitment and differentiation were studied in NB4, a human acute promyelocytic leukemia (APL) cell line. EVI-1 and GATA-1 were stably expressed in NB4 cells by transfection and effects evaluated on granulocyte differentiation induced by all-trans retinoic acid (ATRA). The results showed that EVI-1 expressing NB4 clones differentiate more rapidly and more completely than control clones. In contrast, GATA-1 expressing NB4 clones showed delayed differentiation. These findings demonstrate that EVI-1 expression promotes and GATA-1 expression delays ATRA-induced NB4 cell granulocytic differentiation, suggesting that EVI-1 plays an important role in myeloid differentiation and EVI-1 and GATA-1 antagonize each other in erythroid/myeloid commitment and differentiation.
Degree ProgramGraduate College