title: Ultrasensitive gene regulation by positive feedback loops in nucleosome modification.
abstract: Eukaryotic transcription involves the synergistic interaction of many different proteins. However, the question remains how eukaryotic promoters achieve ultrasensitive or threshold responses to changes in the concentration or activity of a single transcription factor (TF). We show theoretically that by recruiting a histone-modifying enzyme, a TF binding non-cooperatively to a single site can change the balance between opposing positive feedback loops in histone modification to produce a large change in gene expression in response to a small change in concentration of the TF. This mechanism can also generate bistable promoter responses, allowing a gene to be on in some cells and off in others, despite the cells being in identical conditions. In addition, the system provides a simple means by which the activities of many TFs could be integrated at a promoter.
authors.affiliation: Center for Models of Life, Niels Bohr Institute, Blegdamsvej, Copenhagen, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Sneppen
authors.forename: Mille A
authors.initials: MA
authors.lastname: Micheelsen
authors.forename: Ian B
authors.initials: IB
authors.lastname: Dodd
mesh_terms: D002875:Chromosomes / Q000378:metabolism; D044127:Epigenesis, Genetic; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D008954:Models, Biological; D009707:Nucleosomes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D020218:Response Elements; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors