Open AccessUltrasensitive gene regulation by positive feedback loops in nucleosome modification
Author(s) -
Sneppen Kim,
Micheelsen Mille A,
Dodd Ian B
Publication year - 2008
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2008.21
Subject(s) - biology , histone , nucleosome , positive feedback , promoter , transcription factor , bistability , gene , regulation of gene expression , microbiology and biotechnology , gene expression , computational biology , genetics , physics , quantum mechanics , electrical engineering , engineering
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.