SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression.
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.
Wen
Jie
J
National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Huang
Suming
S
Rogers
Heather
H
Dickinson
Liliane A
LA
Kohwi-Shigematsu
Terumi
T
Noguchi
Constance Tom
CT
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002843:Chromatin / Q000502:physiology; D041905:Erythroid Cells / Q000166:cytology* / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005914:Globins / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005810:Multigene Family; D009687:Nuclear Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection
D002843:Chromatin; D036961:Matrix Attachment Region Binding Proteins; D009687:Nuclear Proteins; C076189:SATB1 protein, human; D015534:Trans-Activators; D006427:Hemin; D005914:Globins