title: Transforming ligands into transcriptional regulators: building blocks for bifunctional molecules.
abstract: The human body is comprised of several hundred distinct cell types that all share a common genomic template. This diversity arises from regulated expression of individual genes. The first critical step in this process is transcription and is governed by a large number of transcription factors. Small molecules that can alter transcription hold tremendous utility as chemical probes and therapeutics. To fully realize their potential, however, artificial transcription factors must be able to orchestrate protein recruitment at gene promoters just like their natural counterparts. This tutorial review surveys the discovery of small ligands (drug-like molecules and short peptides) that bind transcriptional coregulatory proteins, and thus comprise one of the two essential characteristics of a transcription factor. By joining these ligands to DNA-targeting moieties, one can construct a bifunctional molecule that recruits its protein target to specific genes and controls gene transcription.
authors.affiliation: Program in Chemical Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jonas W
authors.initials: JW
authors.lastname: Højfeldt
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Van Dyke
authors.forename: Anna K
authors.initials: AK
authors.lastname: Mapp
mesh_terms: D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D056892:Mediator Complex / Q000737:chemistry / Q000378:metabolism; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D008024:Ligands; C492159:MED23 protein, human; D056892:Mediator Complex; D010455:Peptides; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors