Lecturer: Dr. Tamar Friedlander
Affiliation: Institute of Science and Technology,
Austria
Abstract:
Gene activity is mediated by the
specificity of binding interactions between
special proteins, called transcription
factors, and short regulatory sequences on
the DNA, where different protein species
preferentially bind different DNA targets.
Limited interaction specificity may lead to
crosstalk: a regulatory state in which a
gene is either incorrectly activated due to
spurious interactions or remains
erroneously inactive. Since each protein
can potentially interact with numerous
DNA targets, crosstalk is inherently a
global problem, yet has previously not
been studied as such. We construct a
theoretical framework to analyze the
effects of global crosstalk on gene
regulation, using statistical mechanics. We
find that crosstalk in regulatory
interactions puts fundamental limits on the
reliability of gene regulation that are not
easily mitigated by tuning proteins
concentrations or by complex regulatory
schemes proposed in the literature. Our
results suggest that crosstalk imposes a
previously unexplored global constraint on
the functioning and evolution of regulatory
networks, which is qualitatively distinct
from the known constraints that act at the
level of individual gene regulatory
elements. We discuss this problem in the
broader context of combinatorial
explosion of configurations in self-
assembled systems.