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Volume 272, Number 4, Issue of January 24, 1997 pp. 2464-2469
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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GATA-1 DNA Binding Activity Is Down-regulated in Late S Phase in Erythroid Cells

(Received for publication, October 28, 1996)

From the Developmental Biology Research Centre, The Randall Institute, King's College London, 26-29 Drury Lane, London WC2B 5RL, United Kingdom

We have set out to test a model for tissue-specific gene expression that relies on the early replication of expressed genes to sequester limiting activating transcription factors. Using an erythroid cell line, we have tested the changes in the DNA binding activity of the lineage-restricted transcription factor GATA-1 through the cell cycle. We find that GATA-1 activity is low in G₁, peaks in mid-S phase, and then decreases in G₂/M. In contrast, the binding activities of two ubiquitous transcription factors, Oct1 and Sp1, remain high in G₂/M. GATA-1 protein and mRNA vary in a similar manner through the cell cycle, suggesting that the expression of the gene or the stability of its message is regulated. Although a number of transcription factors involved in the control of the cell cycle or DNA replication have been shown to peak in S phase, this is the first example of a lineage-restricted transcription factor displaying S phase-specific DNA binding activity. One interpretation of these data leads to a model in which the peak in GATA-1 DNA binding amplifies the effect of early replication on the activation of erythroid-specific genes at the same time as preventing activation of non-erythroid genes containing GATA-responsive elements. These results may also relate to recent data implicating GATA-1 function in apoptosis and cell cycle progression.

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