Zusammenfassung
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.
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