An erythroid-specific chromatin opening element reorganizes β-globin promoter chromatin structure and augments gene expression

被引:3
|
作者
Nemeth, MJ
Bodine, DM
Garrett, LJ
Lowrey, CH
机构
[1] Dartmouth Coll Sch Med, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA
[2] NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA
[3] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA
[4] Dartmouth Coll Sch Med, Dept Med, Hanover, NH 03755 USA
[5] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA
关键词
D O I
10.1006/bcmd.2001.0448
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In erythroid tissues the chromatin structure of the beta -globin gene locus is extensively remodeled, Changes include the formation of DNase I hypersensitive sites (HSs) over the promoters of actively expressed genes. To test the hypothesis that such "opening" of promoter chromatin structure is important for beta -globin gene expression, we placed a 101-bp erythroid-specific hypersensitive-site forming element (HSFE) from the core of LCR HS4 immediately upstream of a minimal beta -globin gene promoter. We then studied the effects of this element alone and in combination with other cis-acting elements on globin gene chromatin structure and gene expression in MEL cells and transgenic mice. Single or tandem HSFEs increased the size of the portion of the promoter accessible to DNase digestion, increased the proportion of promoters in an accessible conformation, and increased gene expression approximately 5-fold. These were equivalent to expression levels attained using a 2.8-kb mu LCR construct. Inclusion of the LCR HS2 enhancer did not increase expression further. In transgenic mouse fetal liver cells the HSFE increased average expression 2.5-fold compared to the minimal promoter alone. These results indicate that a small cis-acting element is capable of remodeling local beta -globin promoter chromatin structure and producing expression similar to that seen with a mu LCR construct. (C) 2001 Academic Press.
引用
收藏
页码:767 / 780
页数:14
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