RT Journal Article
SR Electronic
T1 Principles of transcription factor traffic on folded chromatin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 164541
DO 10.1101/164541
A1 Ruggero Cortini
A1 Guillaume Filion
YR 2017
UL http://biorxiv.org/content/early/2017/07/17/164541.abstract
AB All organisms regulate the transcription of their genes. To understand this process, it is essential to know how transcription factors find their targets in the genome. In addition to the DNA sequence, several variables have a known influence, but overall the binding patterns of transcription factors distribution remains mostly unexplained in animal genomes. Here we investigate the role of the chromosome conformation in shaping the search path of transcription factors. Using molecular dynamics simulations, we uncover the main principles of their diffusion on folded chromatin. Chromosome contacts play a conflicting role: at low density they enhance the traffic of transcription factors, but a high density they lower the traffic by volume exclusion. Consistently, we observe that in human cells, highly occupied targets, where protein binding is promiscuous, are found at sites engaged in chromosome loops within uncompact chromatin. In summary, those results provide a theoretical framework to understand the search trajectories of transcription factors and highlight the key contribution of genome conformation.