The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo

Funnell, Alister P. W., Norton, Laura J., Mak, Ka Sin, Burdach, Jon, Artuz, Crisbel M., Twine, Natalie A., Wilkins, Marc R., Power, Carl A., Hung, Tzong-Tyng, Perdomo, Jose, Koh, Philip, Bell-Anderson, Kim S., Orkin, Stuart H., Fraser, Stuart T., Perkins, Andrew C., Pearson, Richard C. M. and Crossley, Merlin (2012) The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo. Molecular and Cellular Biology, 32 16: 3281-3292. doi:10.1128/MCB.00173-12

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Author Funnell, Alister P. W.
Norton, Laura J.
Mak, Ka Sin
Burdach, Jon
Artuz, Crisbel M.
Twine, Natalie A.
Wilkins, Marc R.
Power, Carl A.
Hung, Tzong-Tyng
Perdomo, Jose
Koh, Philip
Bell-Anderson, Kim S.
Orkin, Stuart H.
Fraser, Stuart T.
Perkins, Andrew C.
Pearson, Richard C. M.
Crossley, Merlin
Title The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo
Formatted title
The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo
Journal name Molecular and Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
1098-5549
Publication date 2012-08
Sub-type Article (original research)
DOI 10.1128/MCB.00173-12
Open Access Status File (Publisher version)
Volume 32
Issue 16
Start page 3281
End page 3292
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2013
Language eng
Formatted 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.
Keyword Kruppel-like factor
Eklf-null mice
Transcription factor
Beta-thalassemia
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 15 Nov 2012, 15:31:18 EST by System User on behalf of Institute for Molecular Bioscience