Regulation of lineage restricted haemopoietic transcription factors in cell hybrids.
SCL, GATA-1, GATA-2 and GATA-3 encode lineage restricted haemopoietic transcription factors. We have previously shown that SCL, GATA-1 and GATA-2 are expressed in multipotent progenitors prior to lineage commitment, but are down-regulated during granulocyte/monocyte differentiation. The phenomenon of gene extinction in cell hybrids may reveal negative regulatory mechanisms operating during normal differentiation. We have therefore analysed the regulation of SCL, GATA-1, GATA-2 and GATA-3 in cell hybrids formed by the fusion of cell lines representing different haemopoietic lineages. Expression of GATA-3 was extinguished in both human and murine erythroid x T cell hybrids, an observation which suggests that erythroid cells contain factors capable of repressing GATA-3 expression. By contrast expression of SCL, GATA-1 and GATA-2 was not extinguished in erythroid x T or in erythroid x B cell hybrids. These data suggest that T cells and B cells do not contain trans-acting factors capable of down-regulating expression of SCL, GATA-1 or GATA-2, and therefore raise the possibility that a 'hit and run' mechanism may repress these genes during normal haemopoiesis. HpaII sites within the SCL promoter were unmethylated in erythroid cells but methylated in T cells. Erythroid x T and erythroid x B cell hybrids contained both methylated and unmethylated SCL promoters, thus implicating a heritable cis-acting mechanism in the regulation of the SCL gene in lymphoid cell lines. These results provide the first analysis of SCL and GATA gene regulation in stable cell hybrids.
Murrell
A M
AM
University of Cambridge, Department of Haematology, MRC Centre, UK.
Green
A R
AR
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D004912:Erythrocytes / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D006801:Humans; D006822:Hybrid Cells; D008745:Methylation; D051379:Mice; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D015183:Restriction Mapping; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015534:Trans-Activators; D014157:Transcription Factors; C494688:GATA1 protein, human; C494711:GATA2 protein, human; C494749:GATA3 protein, human; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human