Premium
The Effect of the GATA‐1 Transcription Factor in Erythropoiesis.
Author(s) -
White Zach,
Damon Christian,
Pikaart Michael J
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.495.19
Subject(s) - zinc finger , erythropoiesis , gata2 , transcription factor , gata1 , transfection , chemistry , microbiology and biotechnology , gata transcription factor , biology , biochemistry , gene expression , gene , promoter , medicine , anemia
GATA‐1 is a key transcription factor that regulates erythrocyte development and maturation. Studies of lead and GATA‐1 have shown that lead decreases the binding affinity of GATA‐1 to DNA. GATA‐1 contains two zinc binding fingers, one at the N‐terminus and one at the C‐terminus, both of which allow tight GATA protein binding to DNA. In purified GATA protein, lead disrupts a GATA‐1 zinc binding finger by replacing the zinc ion with a lead ion, therefore disrupting the protein's conformation and lowering DNA binding affinity. Our current work addresses the implication of lead interfering with GATA function in living cells. Three different cell culture experiments were conducted to test the effects of lead and DNA binding affinity. First, mouse erythroleukemia (MEL) cells were induced by dimethyl sulfoxide (DMSO) with varying lead concentrations and grown for five days to test levels of hemoglobin expression. Second, quail fibroblast (QT6) cells were effectively transfected with GATA plasmids using cationic lipids with different concentrations of lead to determine GATA expression. Third, pluripotent mouse bone marrow cells were cultured for 48 hours to determine erythroid colony formation. These experiments have shown that the addition of lead inhibits hemoglobin production and GATA‐1 expression and that the GATA zinc fingers may be the location where lead binds and inhibits erythropoiesis.