Human Gene Set: PILON_KLF1_TARGETS_DN


Standard name PILON_KLF1_TARGETS_DN
Systematic name M2228
Brief description Genes down-regulated in erythroid progenitor cells from fetal livers of E13.5 embryos with KLF1 [GeneID=10661] knockout compared to those from the wild type embryos.
Full description or abstract 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.
Collection ARCHIVED: Archived Founder gene sets that are referenced by current Hallmarks
      C2_NONE: ARCHIVED Curated
            C2_CGP: ARCHIVED Chemical and Genetic Perturbations
Source publication Pubmed 18852285   Authors: Pilon AM,Arcasoy MO,Dressman HK,Vayda SE,Maksimova YD,Sangerman JI,Gallagher PG,Bodine DM
Exact source Suppl. File: TERcomparison.xls: green
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Source species Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_Mouse430
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Version history 7.3: Moved to Archive due to mapping changes.


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