Abstract:
:The CACCC-box binding protein erythroid Krüppel-like factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of the gene for a second KLF, basic Krüppel-like factor, or KLF3. We have now tested the in vivo role of KLF3 in erythroid cells by examining Klf3 knockout mice. KLF3-deficient adults exhibit a mild compensated anemia, including enlarged spleens, increased red pulp, and a higher percentage of erythroid progenitors, together with elevated reticulocytes and abnormal erythrocytes in the peripheral blood. Impaired erythroid maturation is also observed in the fetal liver. We have found that KLF3 levels rise as erythroid cells mature to become TER119(+). Consistent with this, microarray analysis of both TER119(-) and TER119(+) erythroid populations revealed that KLF3 is most critical at the later stages of erythroid maturation and is indeed primarily a transcriptional repressor. Notably, many of the genes repressed by KLF3 are also known to be activated by EKLF. However, the majority of these are not currently recognized as erythroid-cell-specific genes. These results reveal the molecular and physiological function of KLF3, defining it as a feedback repressor that counters the activity of EKLF at selected target genes to achieve normal erythropoiesis.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Funnell AP,Norton LJ,Mak KS,Burdach J,Artuz CM,Twine NA,Wilkins MR,Power CA,Hung TT,Perdomo J,Koh P,Bell-Anderson KS,Orkin SH,Fraser ST,Perkins AC,Pearson RC,Crossley Mdoi
10.1128/MCB.00173-12subject
Has Abstractpub_date
2012-08-01 00:00:00pages
3281-92issue
16eissn
0270-7306issn
1098-5549pii
MCB.00173-12journal_volume
32pub_type
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