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Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2.

Publication ,  Journal Article
Pilon, AM; Arcasoy, MO; Dressman, HK; Vayda, SE; Maksimova, YD; Sangerman, JI; Gallagher, PG; Bodine, DM
Published in: Mol Cell Biol
December 2008

Erythroid Krüppel-like factor (EKLF) is a Krüppel-like transcription factor identified as a transcriptional activator and chromatin modifier in erythroid cells. EKLF-deficient (Eklf(-/-)) mice die at day 14.5 of gestation from severe anemia. In this study, we demonstrate that early progenitor cells fail to undergo terminal erythroid differentiation in Eklf(-/-) embryos. To discover potential EKLF target genes responsible for the failure of erythropoiesis, transcriptional profiling was performed with RNA from wild-type and Eklf(-/-) early erythroid progenitor cells. These analyses identified significant perturbation of a network of genes involved in cell cycle regulation, with the critical regulator of the cell cycle, E2f2, at a hub. E2f2 mRNA and protein levels were markedly decreased in Eklf(-/-) early erythroid progenitor cells, which showed a delay in the G(1)-to-S-phase transition. Chromatin immunoprecipitation analysis demonstrated EKLF occupancy at the proximal E2f2 promoter in vivo. Consistent with the role of EKLF as a chromatin modifier, EKLF binding sites in the E2f2 promoter were located in a region of EKLF-dependent DNase I sensitivity in early erythroid progenitor cells. We propose a model in which EKLF-dependent activation and modification of the E2f2 locus is required for cell cycle progression preceding terminal erythroid differentiation.

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Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

December 2008

Volume

28

Issue

24

Start / End Page

7394 / 7401

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Stem Cells
  • Promoter Regions, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Mice, Knockout
  • Mice
  • Liver
  • Kruppel-Like Transcription Factors
  • Gene Regulatory Networks
  • Gene Expression Regulation, Developmental
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pilon, A. M., Arcasoy, M. O., Dressman, H. K., Vayda, S. E., Maksimova, Y. D., Sangerman, J. I., … Bodine, D. M. (2008). Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2. Mol Cell Biol, 28(24), 7394–7401. https://doi.org/10.1128/MCB.01087-08
Pilon, Andre M., Murat O. Arcasoy, Holly K. Dressman, Serena E. Vayda, Yelena D. Maksimova, Jose I. Sangerman, Patrick G. Gallagher, and David M. Bodine. “Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2.Mol Cell Biol 28, no. 24 (December 2008): 7394–7401. https://doi.org/10.1128/MCB.01087-08.
Pilon AM, Arcasoy MO, Dressman HK, Vayda SE, Maksimova YD, Sangerman JI, et al. Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2. Mol Cell Biol. 2008 Dec;28(24):7394–401.
Pilon, Andre M., et al. “Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2.Mol Cell Biol, vol. 28, no. 24, Dec. 2008, pp. 7394–401. Pubmed, doi:10.1128/MCB.01087-08.
Pilon AM, Arcasoy MO, Dressman HK, Vayda SE, Maksimova YD, Sangerman JI, Gallagher PG, Bodine DM. Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2. Mol Cell Biol. 2008 Dec;28(24):7394–7401.

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

December 2008

Volume

28

Issue

24

Start / End Page

7394 / 7401

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Stem Cells
  • Promoter Regions, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Mice, Knockout
  • Mice
  • Liver
  • Kruppel-Like Transcription Factors
  • Gene Regulatory Networks
  • Gene Expression Regulation, Developmental