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

Journal article

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: Papadopoulos, G; Karkoulia, E; Tsamardinos, I; Porcher, C; Ragoussis, J

• Publication status: Published
• Journal: Nucleic acids research
• Volume: 41
• Issue: 9
• Pages: 4938-4948
• Publication date: 2013-05-01
• DOI: 10.1093/nar/gkt167
• EISSN: 1362-4962
• ISSN: 0305-1048
• Language: English
• Keywords: Animals; Liver; Histones; Genome; GATA1 Transcription Factor; Cells, Cultured; Mice; Erythropoiesis; Fetus; Erythroid Cells; Epigenesis, Genetic