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Nucleic Acids Res. 2008 Aug;36(14):4521-8. doi: 10.1093/nar/gkn368. Epub 2008 Jun 27.

The role of transcriptional activator GATA-1 at human beta-globin HS2.

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Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Korea.


GATA-1 is an erythroid activator that binds beta-globin gene promoters and DNase I hypersensitive sites (HSs) of the beta-globin locus control region (LCR). We investigated the direct role of GATA-1 interaction at the LCR HS2 enhancer by mutating its binding sites within minichromosomes in erythroid cells. Loss of GATA-1 in HS2 did not compromise interaction of NF-E2, a second activator that binds to HS2, nor was DNase I hypersensitivity at HS2 or the promoter of a linked epsilon-globin gene altered. Reduction of NF-E2 using RNAi confirmed the overall importance of this activator in establishing LCR HSs. However, recruitment of the histone acetyltransferase CBP and RNA pol II to HS2 was diminished by GATA-1 loss. Transcription of epsilon-globin was severely compromised with loss of RNA pol II from the transcription start site and reduction of H3 acetylation and H3K4 di- and tri-methylation in coding sequences. In contrast, widespread detection of H3K4 mono-methylation was unaffected by loss of GATA-1 in HS2. These results support the idea that GATA-1 interaction in HS2 has a prominent and direct role in co-activator and pol II recruitment conferring active histone tail modifications and transcription activation to a target gene but that it does not, by itself, play a major role in establishing DNase I hypersensitivity.

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