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
相关论文
共 50 条
  • [11] Neuronal expression of zinc finger transcription factor REST/NRSF/XRB gene
    Palm, K
    Belluardo, N
    Metsis, M
    Timmusk, T
    JOURNAL OF NEUROSCIENCE, 1998, 18 (04): : 1280 - 1296
  • [12] Enhancer analysis of the Drosophila zinc finger transcription factor Earmuff by gene targeting
    Kirsten Hildebrandt
    Sabrina Kübel
    Marie Minet
    Nora Fürst
    Christine Klöppel
    Eva Steinmetz
    Uwe Walldorf
    Hereditas, 158
  • [13] Enhancer analysis of the Drosophila zinc finger transcription factor Earmuff by gene targeting
    Hildebrandt, Kirsten
    Kuebel, Sabrina
    Minet, Marie
    Fuerst, Nora
    Kloeppel, Christine
    Steinmetz, Eva
    Walldorf, Uwe
    HEREDITAS, 2021, 158 (01)
  • [14] Activation of the Aspergillus PacC zinc finger transcription factor requires two proteolytic steps
    Díez, E
    Alvaro, J
    Espeso, EA
    Rainbow, L
    Suárez, T
    Tilburn, J
    Arst, HN
    Peñalva, MA
    EMBO JOURNAL, 2002, 21 (06): : 1350 - 1359
  • [15] Finb, a multiple zinc finger protein, represses transcription of the human angiotensinogen gene
    Date, S
    Nibu, Y
    Yanai, K
    Hirata, J
    Yagami, K
    Fukamizu, A
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2004, 13 (05) : 637 - 642
  • [16] TRANSCRIPTION FACTOR REPRESSION AND ACTIVATION OF THE HUMAN ACETYLCHOLINESTERASE GENE
    GETMAN, DK
    MUTERO, A
    INOUE, K
    TAYLOR, P
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (40) : 23511 - 23519
  • [17] Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor
    Ikuta, Togo
    Kawajiri, Kaname
    EXPERIMENTAL CELL RESEARCH, 2006, 312 (18) : 3585 - 3594
  • [18] NEURAL-SPECIFIC EXPRESSION, GENOMIC STRUCTURE, AND CHROMOSOMAL LOCALIZATION OF THE GENE ENCODING THE ZINC-FINGER TRANSCRIPTION FACTOR NGFI-C
    CROSBY, SD
    VEILE, RA
    DONISKELLER, H
    BARABAN, JM
    BHAT, RV
    SIMBURGER, KS
    MILBRANDT, J
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) : 4739 - 4743
  • [19] Transcriptional activation of endogenous gene by a transcription factor, ERF2, in tobacco
    Nakano, T
    Suzuki, K
    Fujimura, T
    Shinshi, H
    PLANT AND CELL PHYSIOLOGY, 2003, 44 : S123 - S123
  • [20] A novel zinc finger structure in the large subunit of human general transcription factor TFIIE
    Okuda, M
    Tanaka, A
    Arai, Y
    Satoh, M
    Okamura, H
    Nagadoi, A
    Hanaoka, F
    Ohkuma, Y
    Nishimura, Y
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (49) : 51395 - 51403