The β-globin LCR is not necessary for an open chromatin structure or developmentally regulated transcription of the native mouse β-globin locus

被引:157
作者
Epner, E
Reik, A
Cimbora, D
Telling, A
Bender, MA
Fiering, S
Enver, T
Martin, DIK
Kennedy, M
Keller, G
Groudine, M
机构
[1] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA
[2] Dartmouth Med Sch, Dept Microbiol, Hanover, NH 03755 USA
[3] Chester Beatty Labs, Leukemia Res Ctr, London SW3 6JB, England
[4] Natl Jewish Med & Res Ctr, Denver, CO 80206 USA
[5] Univ Washington, Sch Med, Dept Radiat Oncol, Seattle, WA 98195 USA
关键词
D O I
10.1016/S1097-2765(00)80144-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The murine beta-globin locus control region (LCR) was deleted from its native chromosomal location. The similar to 25 kb deletion eliminates all sequences and structures homologous to those defined as the human LCR. In differentiated ES cells and erythroleukemia cells containing the LCR-deleted chromosome, DNasel sensitivity of the beta-globin domain is established and maintained, developmental regulation of the locus is intact, and beta-like globin RNA levels are reduced 5%-25% of normal. Thus, in the native murine beta-globin locus, the LCR is necessary for normal levels of transcription, but other elements are sufficient to establish the open chromatin structure, transcription, and developmental specificity of the locus. These findings suggest a contributory rather than dominant function for the LCR in its native location.
引用
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页码:447 / 455
页数:9
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