Erythroid Kruppel-like factor (EKLF) coordinates erythroid cell proliferation and hemoglobinization in cell lines derived from EKLF null mice.
Erythroid Kruppel-like factor (EKLF) is a transcription factor of the C2H2 zinc-finger class that is essential for definitive erythropoiesis. We generated immortal erythroid cell lines from EKLF(-/-) fetal liver progenitor cells that harbor a single copy of the entire human beta-globin locus and then reintroduced EKLF as a tamoxifen-inducible, EKLF-mutant estrogen receptor (EKLF-ER) fusion protein. Addition of tamoxifen resulted in enhanced differentiation and hemoglobinization, coupled with reduced proliferation. Human beta-globin gene expression increased significantly, whereas gamma-globin transcripts remained elevated at levels close to endogenous mouse alpha-globin transcript levels. We conclude that EKLF plays a role in regulation of the cell cycle and hemoglobinization in addition to its role in beta-globin gene expression. The cell lines we used will facilitate structural and functional analyses of EKLF in these processes and provide useful tools for the elucidation of nonglobin EKLF target genes.
Department of Physiology, Monash University, and the Rotary Bone Marrow Research Laboratories, Royal Melbourne Hospital and Melbourne University, Melbourne, Australia.
E
E
Coghill
S
S
Eccleston
V
V
Fox
L
L
Cerruti
C
C
Brown
J
J
Cunningham
S
S
Jane
A
A
Perkins
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D005333:Fetus; D005914:Globins / Q000235:genetics; D006454:Hemoglobins / Q000096:biosynthesis / Q000187:drug effects; D051741:Kruppel-Like Transcription Factors; D008099:Liver / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D014161:Transduction, Genetic
D004268:DNA-Binding Proteins; D006454:Hemoglobins; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D013629:Tamoxifen; D005914:Globins