作者: Rita Ferreira , George Garinis , Nynke Gillemans , Michael Moorhouse , David Whyatt
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摘要: We have previously shown that GATA1 overexpression in erythroid cells inhibits terminal erythroid differentiation, both in vivo and in vitro. However, specific GATA1 functions in terminal erythroid differentiation remain unclear. We employed cDNA microarray technology to analyse the expression profile of GATA1-overexpressing erythroid cells in an attempt to identify putative new GATA1 target genes. We started by analysing the gene expression profile of GATA1-overexpressing cells in vivo, using the GATA1 overexpressing transgenic mouse model previously generated in our laboratory. Transgenic female (TgF) embryos, expressing the transgene in approximately 50% of the erythroid cells, survive to adulthood but transgenic male (TgM) embryos, expressing the transgene in all the erythroid cells, die from anemia around embryonic day 13.5 (E13. 5). Using E12. 5 fetal livers from TgF, TgM and wild type (WT) embryos we identified 744 differentially expressed genes. Of these 18% were differentially expressed in both TgF and TgM. The remaining genes were differentially expressed in either TgF (26%) or TgM (56%). Differentially expressed genes were classified in agreement with their known role in particular physiological processes according to the Gene Ontology (GO) classification system. In a first analysis we identified particular physiological processes containing larger number of differentially expressed genes that correlate well with the known GATA1 functions in proliferation/differentiation, regulation of transcription and apoptosis. Since variation is high between embryos we continued our analysis using and in vitro model system. GATA1 …