Step into the groove: engineered transcription factors as modulators of gene expression.
Increasing knowledge about the influence of dysregulated gene expression in causing numerous diseases opens up new possibilities for the development of innovative therapeutics. In this chapter, we first describe different mechanisms of misregulated gene expression resulting in various pathophysiological conditions. Then, an overview is given of different technologies developed to readjust expression levels of genes. One of the most promising upcoming approaches in this respect is the development of engineered zinc-finger transcription factors. Results obtained from modulating endogenous gene expression using such engineered transcription factors are reviewed in depth. Finally, we address possible pitfalls of using such transcriptional targeting approaches at the "chromatin level." We describe aspects of studies at this level that influence successful DNA binding of engineered transcription factors, thereby affecting gene activity. Engineered transcription factors have great promise as potent therapeutics. Moreover, this technology is expected to yield fundamental knowledge about the organization and function of the genome.
Visser
Astrid E
AE
Department of Molecular Genetics, Leiden Institute of Chemistry, University of Leiden, 2300 RA Leiden, The Netherlands.
Verschure
Pernette J
PJ
Gommans
Willemijn M
WM
Haisma
Hidde J
HJ
Rots
Marianne G
MG
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009707:Nucleosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D034622:RNA Interference; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D009707:Nucleosomes; D014157:Transcription Factors