Synthetic zinc finger transcription factor action at an endogenous chromosomal site - Activation of the human erythropoietin gene

被引:144
|
作者
Zhang, L [1 ]
Spratt, SK [1 ]
Liu, Q [1 ]
Johnstone, B [1 ]
Qi, H [1 ]
Raschke, EE [1 ]
Jamieson, AC [1 ]
Rebar, EJ [1 ]
Wolffe, AP [1 ]
Case, CC [1 ]
机构
[1] Sangamo Biosci Inc, Point Richmond Tech Ctr, Richmond, CA 94804 USA
关键词
D O I
10.1074/jbc.M005341200
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
We have targeted the activation of an endogenous chromosomal locus including the human erythropoietin gene using synthetic transcription factors. These transcription factors are targeted to particular DNA sequences in the 5'-flanking region of the erythropoietin gene through engineering of a zinc finger DNA binding domain. The DNA binding domain is linked to a VP16 transcriptional activation domain. We find that these synthetic transcription factors invariably activate transiently transfected templates in which sequences within the 5' flank of the erythropoietin gene are fused to a luciferase reporter. The efficiency of activation under these circumstances at a defined site is dependent on DNA binding affinity. In contrast, only a subset of these same zinc finger proteins is able to activate the endogenous chromosomal locus. The activity of these proteins is influenced by their capacity to gain access to their recognition elements within the chromatin infrastructure, Zinc finger transcription factors will provide a powerful tool to probe the determinants of chromatin accessibility and remodeling within endogenous chromosomal loci.
引用
收藏
页码:33850 / 33860
页数:11
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