title: GATA-1 genome-wide occupancy associates with distinct epigenetic profiles in mouse fetal liver erythropoiesis.
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.
authors.affiliation: Division of Molecular Oncology, Biomedical Sciences Research Center "Alexander Fleming", Vari GR16672, Greece.
authors.forename: Giorgio L
authors.initials: GL
authors.lastname: Papadopoulos
authors.forename: Elena
authors.initials: E
authors.lastname: Karkoulia
authors.forename: Ioannis
authors.initials: I
authors.lastname: Tsamardinos
authors.forename: Catherine
authors.initials: C
authors.lastname: Porcher
authors.forename: Jiannis
authors.initials: J
authors.lastname: Ragoussis
authors.forename: Jörg
authors.initials: J
authors.lastname: Bungert
authors.forename: John
authors.initials: J
authors.lastname: Strouboulis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D041905:Erythroid Cells / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics*; D005333:Fetus; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D016678:Genome; D006657:Histones / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D051379:Mice
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D006657:Histones