Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells.
The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid, megakaryocyte, and mast cell lineages. GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes. Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation. Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development. Efficient rescue of the defect requires an intact GATA element in the distal promoter, suggesting autoregulatory control of GATA-1 transcription. To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop, we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei. We show here that proerythroblasts and mature erythroid cells contain a diffusible activity (TAG) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells. Nuclei from GATA-1- mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons, indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion.
Baron
M H
MH
Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138.
Farrington
S M
SM
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D015870:Gene Expression; D005786:Gene Expression Regulation; D005914:Globins / Q000096:biosynthesis; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013234:Stem Cells; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C494689:Gata1 protein, mouse; D014157:Transcription Factors; D005914:Globins