EKLF and KLF2 have compensatory roles in embryonic globin gene expression and primitive erythropoiesis

Basu, P.; Lemsaddek, Wafaa; Sargent, Thanh Giang; Lung, Tina K.; Basu, Mohua; Lingrel, Jerry B.; Haar, Jack L.; Lloyd, Joyce A.

doi:10.1016/j.bcmd.2006.10.084

Cited by 21 publications

(31 citation statements)

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“…KLF1 and KLF2 can partially compensate for each other, as is evident from the reduced embryonic b-like globin gene expression of KLF1/KLF2 double (KLF1-/-KLF2-/-) compared to single knockout embryos. 11 There is also more aberrant morphology, consistent with increased apoptosis, in double compared to single knockout primitive red blood cells.…”

Section: Introductionmentioning

confidence: 95%

“…A model with the KLF1 and KLF2 null alleles on the same chromosome, KLF1+/-KLF2+/-(R), was developed. 11 Mice with a floxed KLF2 allele were obtained from Dr. Jerry Lingrel. 30 Mice carrying the KLF1 null allele and the KLF2 floxed allele on the same chromosome were created by screening for recombinants as previously described.…”

Section: Generation Of Micementioning

confidence: 99%

“…30 Mice carrying the KLF1 null allele and the KLF2 floxed allele on the same chromosome were created by screening for recombinants as previously described. 11 The Tie2-Cre mouse model has been described previously. 31 All experiments involving mice were approved by the Virginia Commonwealth University Institutional Animal Care and Use Committee (VCU IACUC) under protocol number AM10347.…”

Section: Generation Of Micementioning

confidence: 99%

“…KLF2 is necessary for primitive erythropoiesis, and positively regulates embryonic globin gene expression, as shown in KLF2 knockout and erythroid-conditional knockout mouse embryos. 11,19,20 Global gene expression assays indicate that many genes that are important in the processes of development, differentiation and cell migration are dysregulated in KLF2-/-compared to wild-type primitive erythroid cells. 21 Ablation of KLF2 causes lethality between E11.5 and E14.…”

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: Introductionmentioning

confidence: 95%

Section: Generation Of Micementioning

confidence: 99%

Section: Generation Of Micementioning

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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Identification of erythroid‐enriched gene expression in the mouse embryonic yolk sac using microdissected cells

Redmond

Dumur

Archer

et al. 2008

Developmental Dynamics

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Little is known about the genes that control the embryonic erythroid program. Laser capture microdissection was used to isolate primitive erythroid precursors and epithelial cells from frozen sections of the embryonic day 9.5 yolk sac. The RNA samples were amplified and labeled for hybridization to Affymetrix GeneChip Mouse Genome 430A 2.0 arrays. Ninety-one genes are expressed significantly higher in erythroid than in epithelial cells. Ingenuity pathway analysis indicates that many of these erythroidenriched genes cluster in highly significant biological networks. One of these networks contains RBTN2/LMO2, SCL/TAL1, and EKLF/KLF1, three of the very few genes required for primitive erythropoiesis. Quantitative real-time polymerase chain reaction was used to verify that platelet factor 4, reelin, thrombospondin-1, and muscleblind-like 1 mRNA is erythroid-enriched. These genes have established roles in development or differentiation in other systems, and are, therefore, good candidates for regulating primitive erythropoiesis. These results provide a catalog of genes expressed during primitive erythropoiesis. Developmental Dynamics 237:436 -446, 2008.

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Protein–protein interactions: Analysis of a false positive GST pulldown result

et al. 2011

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One of the most common ways to demonstrate a direct protein-protein interaction in vitro is the glutathione-S-transferse (GST)-pulldown. Here we report the detailed characterization of a putative interaction between two transcription factor proteins, GATA-1 and Krüppel-like factor 3 (KLF3/BKLF) that show robust interactions in GST-pulldown experiments. Attempts to map the interaction interface of GATA-1 on KLF3 using a mutagenic screening approach did not yield a contiguous binding face on KLF3, suggesting that the interaction might be non-specific. NMR experiments showed that the proteins do not interact at protein concentrations of 50-100 μM. Rather, the GST tag can cause part of KLF3 to misfold. In addition to misfolding, the fact that both proteins are DNA-binding domains appears to introduce binding artifacts (possibly nucleic acid bridging) that cannot be resolved by the addition of nucleases or ethidium bromide (EtBr). This study emphasizes the need for caution in relying on GST-pulldown results and related methods, without convincing confirmation from different approaches.

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EKLF and KLF2 have compensatory roles in embryonic globin gene expression and primitive erythropoiesis

Cited by 21 publications

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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

Identification of erythroid‐enriched gene expression in the mouse embryonic yolk sac using microdissected cells

Protein–protein interactions: Analysis of a false positive GST pulldown result

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