title: Human zinc fingers as building blocks in the construction of artificial transcription factors.
abstract: We describe methods for generating artificial transcription factors capable of up- or downregulating the expression of genes whose promoter regions contain the target DNA sequences. To accomplish this, we screened zinc fingers derived from sequences in the human genome and isolated 56 zinc fingers with diverse DNA-binding specificities. We used these zinc fingers as modular building blocks in the construction of novel, sequence-specific DNA-binding proteins. Fusion of these zinc-finger proteins with either a transcriptional activation or repression domain yielded potent transcriptional activators or repressors, respectively. These results show that the human genome encodes zinc fingers with diverse DNA-binding specificities and that these domains can be used to design sequence-specific DNA-binding proteins and artificial transcription factors.
authors.affiliation: ToolGen Inc., 461-6 Jeonmin-Dong, Yusung-Gu, Daejeon, 305-390, South Korea.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Bae
authors.forename: Young Do
authors.initials: YD
authors.lastname: Kwon
authors.forename: Hyun-Chul
authors.initials: HC
authors.lastname: Shin
authors.forename: Moon-Sun
authors.initials: MS
authors.lastname: Hwang
authors.forename: Eun-Hyun
authors.initials: EH
authors.lastname: Ryu
authors.forename: Kyung-Soon
authors.initials: KS
authors.lastname: Park
authors.forename: Hyo-Young
authors.initials: HY
authors.lastname: Yang
authors.forename: Dong-Ki
authors.initials: DK
authors.lastname: Lee
authors.forename: Yangsoon
authors.initials: Y
authors.lastname: Lee
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Park
authors.forename: Heung Sun
authors.initials: HS
authors.lastname: Kwon
authors.forename: Hyun-Won
authors.initials: HW
authors.lastname: Kim
authors.forename: Byung-Il
authors.initials: BI
authors.lastname: Yeh
authors.forename: Hyean-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Soon Hyung
authors.initials: SH
authors.lastname: Sohn
authors.forename: Joonho
authors.initials: J
authors.lastname: Yoon
authors.forename: Wongi
authors.initials: W
authors.lastname: Seol
authors.forename: Jin-Soo
authors.initials: JS
authors.lastname: Kim
mesh_terms: D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D019151:Peptide Library; D015202:Protein Engineering / Q000379:methods; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic; D015003:Yeasts / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D019151:Peptide Library; D011994:Recombinant Proteins; D014157:Transcription Factors; D004247:DNA