Krüppel-Like Factor 1 (KLF1), KLF2, and Myc Control a Regulatory Network Essential for Embryonic Erythropoiesis

Pang, Christopher J.; Lemsaddek, Wafaa; Alhashem, Yousef N.; Bondzi, Cornelius; Redmond, Latasha C.; Ah-Son, Nicolas; Dumur, Catherine I.; Archer, Kellie J.; Haar, Jack L.; Lloyd, Joyce A.; Trudel, Marie

doi:10.1128/mcb.00104-12

Cited by 35 publications

(35 citation statements)

References 82 publications

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“…12 In order to understand the contributions of KLF1 and KLF2 to the starkly different erythropoietic phenotypes of E10.5 KLF1+/-KLF2-/-and KLF1-/-KLF2+/-embryos, circulating blood cell numbers were determined. KLF1-/-KLF2+/-, KLF1+/-KLF2-/-and KLF1-/-KLF2-/-embryos have fewer peripheral blood cells than wild-type ( Figure 3C).…”

Section: E105 Klf1+/-klf2-/-and Klf1-/-klf2-/-embryos Have Fewer Permentioning

confidence: 99%

“…12 Therefore, qRT-PCR was used to assess expression of these genes in wild-type, KLF1-/-KLF2+/-, KLF1+/KLF2-/-and KLF1-/-KLF2-/-E10. Figure 6A), specifically correlating with the genotypes that display the anemia phenotype and reduced peripheral blood cell number.…”

Section: Klf1 and Klf2 Modulate The Expression Of Genes Controling Prmentioning

confidence: 99%

“…12 These genes are principally involved in cellular pathways that control homeostasis, hemopoiesis, apoptosis and proliferation. Erythroid conditional knockout and other functional studies identified Myc as an important downstream target of KLF1 and KLF2.…”

Section: Introductionmentioning

confidence: 99%

“…cDNA synthesis and quantitative reverse-transcriptase PCR (qRT-PCR) were performed as previously described. 11,12,19,20 Primer sequences for qRT-PCR are listed in Online Supplementary Table S1.…”

mentioning

confidence: 99%

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Kruppel-like transcription factors KLF1 and KLF2 have unique and coordinate roles in regulating embryonic erythroid precursor maturation

et al. 2014

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The Krüppel-like transcription factors KLF1 and KLF2 are essential for embryonic erythropoiesis. They can partially compensate for each other during mouse development, and coordinately regulate numerous erythroid genes, including the b-like globins. Simultaneous ablation of KLF1 and KLF2 results in earlier embryonic lethality and severe anemia. In this study, we determine that this anemia is caused by a paucity of blood cells, and exacerbated by diminished b-like globin gene expression. The anemia phenotype is dose-dependent, and, interestingly, can be ameliorated by a single copy of the KLF2, but not the KLF1 gene. The roles of KLF1 and KLF2 in maintaining normal peripheral blood cell numbers and globin mRNA amounts are erythroid cell-specific. Mechanistic studies led to the discovery that KLF2 has an essential function in erythroid precursor maintenance. KLF1 can partially compensate for KLF2 in this role, but is uniquely crucial for erythroid precursor proliferation through its regulation of G1-to S-phase cell cycle transition. A more drastic impairment of primitive erythroid colony formation from embryonic progenitor cells occurs with simultaneous loss of KLF1 and KLF2 than with loss of a single factor. KLF1 and KLF2 coordinately regulate several proliferation-associated genes, including Foxm1. Differential expression of FoxM1, in particular, correlates with the observed KLF1 and KLF2 gene dosage effects on anemia. Furthermore, KLF1 binds to the FoxM1 gene promoter in blood cells. Thus KLF1 and KLF2 coordinately regulate embryonic erythroid precursor maturation through the regulation of multiple homeostasis-associated genes, and KLF2 has a novel and essential role in this process.

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Section: E105 Klf1+/-klf2-/-and Klf1-/-klf2-/-embryos Have Fewer Permentioning

confidence: 99%

Section: Klf1 and Klf2 Modulate The Expression Of Genes Controling Prmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Kruppel-like transcription factors KLF1 and KLF2 have unique and coordinate roles in regulating embryonic erythroid precursor maturation

et al. 2014

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“…The transcription factor erythroid Kruppel-like factor (EKLF/KLF1) plays a crucial function during erythropoiesis (12). EKLF/KLF1 and KLF2 bind the c-Myc (Myc) promoter and regulate expression of the Myc gene (13). Down-regulation of Myc expression at the late stage of erythropoiesis is essential for terminal erythroid maturation (14).…”

mentioning

confidence: 99%

α-1,6-Fucosyltransferase (FUT8) Inhibits Hemoglobin Production during Differentiation of Murine and K562 Human Erythroleukemia Cells

Sasaki

Toda

Furukawa

et al. 2013

Journal of Biological Chemistry

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Background:The overall view of erythropoiesis remains unclear. Results: Overexpression of ␣-1,6-fucosyltransferase inhibits hemoglobin production in murine and human erythroleukemia cells; down-regulation of ␣-1,6-fucosyltransferase promotes hemoglobin production and erythroid differentiation of human erythroleukemia cells. Conclusion: Core fucosylation plays an important role in hemoglobin production and erythroid differentiation. Significance: This might be the first finding that glycosylation negatively regulates erythroid differentiation.

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Biology of human primitive erythroblasts for application in noninvasive prenatal diagnosis

et al. 2018

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Krüppel-Like Factor 1 (KLF1), KLF2, and Myc Control a Regulatory Network Essential for Embryonic Erythropoiesis

Cited by 35 publications

References 82 publications

Kruppel-like transcription factors KLF1 and KLF2 have unique and coordinate roles in regulating embryonic erythroid precursor maturation

Kruppel-like transcription factors KLF1 and KLF2 have unique and coordinate roles in regulating embryonic erythroid precursor maturation

α-1,6-Fucosyltransferase (FUT8) Inhibits Hemoglobin Production during Differentiation of Murine and K562 Human Erythroleukemia Cells

Biology of human primitive erythroblasts for application in noninvasive prenatal diagnosis

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