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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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RED CELLS
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 Tom Noguchi
From the Laboratory of Chemical Biology and Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; and Department of Cell and Molecular Biology, Lawrence Berkeley National Laboratory, Berkeley, CA.
Special AT-rich binding protein 1 (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 down-regulates SATB1 family protein and -globin gene expression. Chromatin immunoprecipitation using anti-SATB1 anti-body 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 cotransfection experiments, increase in -promoter activity by SATB1 was amplified by CBP and blocked by E1A, a CBP inhibitor. Our results suggest that SATB1 can up-regulate 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. (Blood. 2005;105:3330-3339)
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