Transcriptomics

Dataset Information

0

Mechanisms of terminal erythroid differentiation defect in EKLF-deficient mice


ABSTRACT: 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 differention 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 G1-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. RNA was isolated from flow-sorted early erythroid progenitors in 13.5 day old fetal livers from EKLF knock out mice (n=3 fetal livers) and wild-type control mice (n=3 fetal livers) for gene expression analysis

ORGANISM(S): Mus musculus  

SUBMITTER: Holly Kloos Dressman   M O Arcasoy  D M Bodine  J I Sangerman  A M Pilon  H K Dressman  S E Vayda  Y D Maksimova  P G Gallagher 

PROVIDER: E-GEOD-36618 | ArrayExpress | 2012-03-20

SECONDARY ACCESSION(S): GSE36618PRJNA153703

REPOSITORIES: GEO, ArrayExpress

Similar Datasets

2013-06-17 | E-GEOD-48020 | ArrayExpress
2013-06-14 | E-GEOD-46108 | ArrayExpress
2011-12-31 | E-GEOD-30809 | ArrayExpress
2014-08-09 | E-GEOD-60136 | ArrayExpress
2011-12-31 | E-GEOD-30808 | ArrayExpress
2008-10-20 | E-GEOD-10584 | ArrayExpress
2012-01-06 | E-GEOD-30279 | ArrayExpress
2012-04-01 | E-GEOD-33979 | ArrayExpress
2012-05-31 | E-GEOD-37869 | ArrayExpress
2007-09-04 | E-GEOD-2527 | ArrayExpress