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Molecular and Cellular Biology, February 2003, p. 1334-1340, Vol. 23, No. 4
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.4.1334-1340.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Formation of a Tissue-Specific Histone Acetylation Pattern by the Hematopoietic Transcription Factor GATA-1

Division of Hematology, Children's Hospital of Philadelphia,¹ University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104²

Received 5 September 2002/ Returned for modification 14 October 2002/ Accepted 21 November 2002

One function of lineage-restricted transcription factors may be to control the formation of tissue-specific chromatin domains. In erythroid cells, the ß-globin gene cluster undergoes developmentally regulated hyperacetylation of histones at the active globin genes and the locus control region (LCR). However, it is unknown which transcription factor(s) governs the establishment of this erythroid-specific chromatin domain. We measured histone acetylation at the ß-globin locus in the erythroid cell line G1E, which is deficient for the essential hematopoietic transcription factor GATA-1. Restoration of GATA-1 activity in G1E cells led to a substantial increase in acetylation of histones H3 and H4 at the ß-globin promoter and the LCR. Time course experiments showed that histone acetylation occurred rapidly after GATA-1 activation and coincided with globin gene expression, indicating that the effects of GATA-1 are direct. Moreover, increases in histone acetylation correlated with occupancy of GATA-1 and the acetyltransferase CBP at the locus in vivo. Together, these results suggest that GATA-1 and its cofactor CBP are essential for the formation of an erythroid-specific acetylation pattern that is permissive for high levels of gene expression.

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