Small-molecule regulators that mimic transcription factors

Rodríguez‐Martínez, José A.; Peterson‐Kaufman, Kimberly J.; Ansari, Aseem Z.

doi:10.1016/j.bbagrm.2010.08.010

Cited by 27 publications

(35 citation statements)

References 110 publications

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“…In an effort to understand and control desired gene networks, synthetic and chemical biologists have engineered small molecules and proteins to mimic the sequence specificity and regulatory properties of natural DNA-binding factors (Ansari and Mapp, 2002;Dervan et al, 2005;Gonzalez et al, 2010;Gottesfeld et al, 2000;Lee and Mapp, 2010;Mapp and Ansari, 2007;Rodríguez-Martínez et al, 2010;Sera, 2010;Wolfe et al, 2000). Defining the DNA sequence specificity of these engineered molecules is an important step in targeted regulation of genes and networks.…”

Section: Introductionmentioning

confidence: 99%

Sequence-Specificity and Energy Landscapes of DNA-Binding Molecules

Tietjen¹,

Donato²,

Bhimisaria³

et al. 2011

Methods in Enzymology

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Section: Introductionmentioning

confidence: 99%

Sequence-Specificity and Energy Landscapes of DNA-Binding Molecules

Tietjen¹,

Donato²,

Bhimisaria³

et al. 2011

Methods in Enzymology

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“…For example, in vitro DBPs of TFs can be used to guide the design and selection of artificial TFs (Gommans et al 2005, Klug 2005, small molecules of TF mimics (Kwon et al 2004, Xiao et al 2007, Block et al 2009, Rodriguez-Martinez et al 2010, Kushal et al 2011, and TF decoys (Penolazzi et al 2007, Tomita et al 2007, which can be developed as drugs for transcription therapy. The in vitro DBPs can also accelerate the creation of precisiontailored DNA therapeutics (Carlson et al 2010).…”

Section: Dsdna Microarraymentioning

confidence: 99%

In vitro DNA-binding profile of transcription factors: methods and new insights

Wang¹,

Lü²,

Gu³

et al. 2011

Journal of Endocrinology

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The DNA-binding specificity of transcription factors (TFs) has broad impacts on cell physiology, cell development and in evolution. However, the DNA-binding specificity of most known TFs still remains unknown. The specificity of a TF protein is determined by its relative affinity to all possible binding sites. In recent years, the development of several in vitro techniques permits high-throughput determination of relative binding affinity of a TF to all possible k bp-long DNA sequences, thus greatly promoting the characterization of DNA-binding specificity of many known TFs. All DNA sequences that can be bound by a TF with various binding affinities form their DNA-binding profile (DBP). The DBP is important to generate an accurate DNA-binding model, identify all DNA-binding sites and target genes of TFs in the whole genome, and build transcription regulatory network. This study reviewed these techniques, especially two master techniques: double-stranded DNA microarray and systematic evolution of ligands by exponential enrichment in combination with parallel DNA sequencing techniques (SELEX-seq).

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“…Their stability and resistance to enzymatic degradation in cells have made PNAs attractive DNA-binding modules in designing synthetic ATFs. Of synthetic DBDs, minor groove-binding polyamides have emerged as the most reliable class of molecules that can be rationally designed to target desired DNA sequences [41]. Although polyamides can serve as effective DBDs, there still lies a challenge in delivery to the nucleus.…”

Section: Toolbox and Modular Designmentioning

confidence: 99%

“…Minor groove-binding polyamides are a class of molecules that can be rationally designed to target desired DNA sequences [41]. In Nature, Actinobacteria produce the small molecule antibiotics distamycin and netropsin that bind to AT-rich DNA [87,88].…”

Section: Figurementioning

confidence: 99%

Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers

Eguchi

Lee

Wan

et al. 2014

Biochemical Journal

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Transcription factors control the fate of a cell by regulating the expression of genes and regulatory networks. Recent successes in inducing pluripotency in terminally differentiated cells as well as directing differentiation with natural transcription factors has lent credence to the efforts that aim to direct cell fate with rationally designed transcription factors. Because DNA-binding factors are modular in design, they can be engineered to target specific genomic sequences and perform pre-programmed regulatory functions upon binding. Such precision-tailored factors can serve as molecular tools to reprogramme or differentiate cells in a targeted manner. Using different types of engineered DNA binders, both regulatory transcriptional controls of gene networks, as well as permanent alteration of genomic content, can be implemented to study cell fate decisions. In the present review, we describe the current state of the art in artificial transcription factor design and the exciting prospect of employing artificial DNA-binding factors to manipulate the transcriptional networks as well as epigenetic landscapes that govern cell fate.

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Small-molecule regulators that mimic transcription factors

Cited by 27 publications

References 110 publications

Sequence-Specificity and Energy Landscapes of DNA-Binding Molecules

Sequence-Specificity and Energy Landscapes of DNA-Binding Molecules

In vitro DNA-binding profile of transcription factors: methods and new insights

Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers

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