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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3330-3339.
Prepublished online as a Blood First Edition Paper on December 23, 2004; DOI 10.1182/blood-2004-08-2988.
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Submitted August 9, 2004
Accepted December 10, 2004
SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression
Jie Wen, Suming Huang, Heather Rogers, Liliane A Dickinson, Terumi Kohwi-Shigematsu, and Constance T Noguchi*
Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
Department of Cell and Molecular Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
* Corresponding author; email: cnoguchi{at}helix.nih.gov.
SATB1 nuclear protein, expressed predominantly in T-cells, regulates genes through targeting chromatin remodeling during T-cell maturation. Here we show SATB1 family protein induction during early human adult erythroid progenitor cell differentiation concomitant with -globin expression. Erythroid differentiation of human erythroleukemia K562 cells by hemin simultaneously increases -globin and downregulates SATB1 family protein and -globin gene expression. Chromatin immunoprecipitation (ChIP) using anti-SATB1 antibody shows selective binding in vivo in the -globin cluster to the hypersensitive site 2 (HS2) in the locus control region (LCR) and to the -globin promoter. SATB1 overexpression increases -globin and decreases -globin gene expression accompanied by histone hyperacetylation and hypomethylation in chromatin from the -globin promoter and HS2, and histone hypoacetylation and hypermethylation associated with the -globin promoter. In K562 cells SATB1 family protein forms a complex with CREB-binding protein (CBP) important in transcriptional activation. In co-transfection experiments, increase in -promoter activity by SATB1 was amplified by CBP and blocked by E1A, a CBP inhibitor. Our results suggest that SATB1 can upregulate the -globin gene by interaction with specific sites in the -globin cluster and imply that SATB1 family protein expressed in the erythroid progenitor cells may have a role in globin gene expression during early erythroid differentiation.

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