GATA-1 genome-wide occupancy associates with distinct epigenetic profiles in mouse fetal liver erythropoiesis

Giorgio L Papadopoulos, Elena Karkoulia, Ioannis Tsamardinos, Catherine Porcher, Jiannis Ragoussis, Jörg Bungert, John Strouboulis

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

We report the genomic occupancy profiles of the key hematopoietic transcription factor GATA-1 in pro-erythroblasts and mature erythroid cells fractionated from day E12.5 mouse fetal liver cells. Integration of GATA-1 occupancy profiles with available genome-wide transcription factor and epigenetic profiles assayed in fetal liver cells enabled as to evaluate GATA-1 involvement in modulating local chromatin structure of target genes during erythroid differentiation. Our results suggest that GATA-1 associates preferentially with changes of specific epigenetic modifications, such as H4K16, H3K27 acetylation and H3K4 di-methylation. Furthermore, we used random forest (RF) non-linear regression to predict changes in the expression levels of GATA-1 target genes based on the genomic features available for pro-erythroblasts and mature fetal liver-derived erythroid cells. Remarkably, our prediction model explained a high proportion of 62% of variation in gene expression. Hierarchical clustering of the proximity values calculated by the RF model produced a clear separation of upregulated versus downregulated genes and a further separation of downregulated genes in two distinct groups. Thus, our study of GATA-1 genome-wide occupancy profiles in mouse primary erythroid cells and their integration with global epigenetic marks reveals three clusters of GATA-1 gene targets that are associated with specific epigenetic signatures and functional characteristics.

Original languageEnglish
Pages (from-to)4938-48
Number of pages11
JournalNucleic Acids Research
Volume41
Issue number9
DOIs
Publication statusPublished - May 2013

Keywords

  • Animals
  • Cells, Cultured
  • Epigenesis, Genetic
  • Erythroid Cells/metabolism
  • Erythropoiesis/genetics
  • Fetus
  • GATA1 Transcription Factor/metabolism
  • Genome
  • Histones/metabolism
  • Liver/cytology
  • Mice

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