Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Chemically regulated zinc finger transcription factors

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Beerli, R. R.
  • Schopfer, U.
  • Dreier, B.
  • Barbas III, Carlos

publication date

  • October 2000

journal

  • Journal of Biological Chemistry  Journal

abstract

  • Ligand-dependent transcriptional regulators were generated by fusion of designed Cys(2)-His(2) zinc finger proteins and steroid hormone receptor ligand binding domains. To produce novel DNA binding domains, three-finger proteins binding specific 9-base pair sequences were constructed from modular building blocks. Fusion of these zinc finger proteins to a transcriptional activation domain and to modified ligand binding domains derived from either the estrogen or progesterone receptors yielded potent ligand-dependent transcriptional regulators. Together with optimized minimal promoters, these regulators provide 4-hydroxytamoxifen- or RU486-inducible expression systems with induction ratios of up to 3 orders of magnitude. These inducible expression systems are functionally independent, and each can be selectively switched on within the same cell. The potential use of zinc finger-steroid receptor fusion proteins for the regulation of natural promoters was also explored. A gene-specific six-finger protein binding an 18-base pair target sequence was converted into a ligand-dependent regulator by fusion with either two estrogen receptor ligand binding domains or one ecdysone receptor and one retinoid X receptor ligand binding domain. These single-chain receptor proteins undergo an intramolecular rearrangement, rather than intermolecular dimerization and are functional as monomers. Thus, the ability to engineer DNA binding specificities of zinc finger proteins enables the construction of ligand-dependent transcriptional regulators with potential for the regulation of virtually any desired artificial or natural promoter. It is anticipated that the novel chemically regulated gene switches described herein will find many applications in applied and basic research, where the specific modulation of gene expression can be exploited.

subject areas

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Carrier Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Genetic Variation
  • Humans
  • Immediate-Early Proteins
  • Ligands
  • Luciferases
  • Maltose-Binding Proteins
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Receptors, Retinoic Acid
  • Recombinant Fusion Proteins
  • Repetitive Sequences, Nucleic Acid
  • Retinoid X Receptors
  • Substrate Specificity
  • TATA Box
  • Transcription Factors
  • Transcription, Genetic
  • Zinc Fingers
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M005108200

PubMed ID

  • 10924515
scroll to property group menus

Additional Document Info

start page

  • 32617

end page

  • 32627

volume

  • 275

issue

  • 42

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support