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 
epsilon-globin expression. Erythroid differentiation of human erythroleukemia 
K562 cells by hemin simultaneously increases gamma-globin and down-regulates 
SATB1 family protein and epsilon-globin gene expression. Chromatin 
immunoprecipitation using anti-SATB1 anti-body shows selective binding in vivo 
in the beta-globin cluster to the hypersensitive site 2 (HS2) in the locus 
control region (LCR) and to the epsilon-globin promoter. SATB1 overexpression 
increases epsilon-globin and decreases gamma-globin gene expression accompanied 
by histone hyperacetylation and hypomethylation in chromatin from the 
epsilon-globin promoter and HS2, and histone hypoacetylation and 
hypermethylation associated with the gamma-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 
epsilon-promoter activity by SATB1 was amplified by CBP and blocked by E1A, a 
CBP inhibitor. Our results suggest that SATB1 can up-regulate the epsilon-globin 
gene by interaction with specific sites in the beta-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.