Dissecting the logical types of network control in gene expression profiles

Carsten Marr,Georgi Muskhelishvili,Marcel Geertz,Marc-Thorsten Hütt

doi:10.1186/1752-0509-2-18

Carsten Marr, Georgi Muskhelishvili + Show 2 more

Open Access

https://doi.org/10.1186/1752-0509-2-18

Copy DOI

Abstract

BackgroundIn the bacterium Escherichia coli the transcriptional regulation of gene expression involves both dedicated regulators binding specific DNA sites with high affinity and also global regulators – abundant DNA architectural proteins of the bacterial nucleoid binding multiple sites with a wide range of affinities and thus modulating the superhelical density of DNA. The first form of transcriptional regulation is predominantly pairwise and specific, representing digitial control, while the second form is (in strength and distribution) continuous, representing analog control.ResultsHere we look at the properties of effective networks derived from significant gene expression changes under variation of the two forms of control and find that upon limitations of one type of control (caused e.g. by mutation of a global DNA architectural factor) the other type can compensate for compromised regulation. Mutations of global regulators significantly enhance the digital control, whereas in the presence of global DNA architectural proteins regulation is mostly of the analog type, coupling spatially neighboring genomic loci. Taken together our data suggest that two logically distinct – digital and analog – types of control are balancing each other.ConclusionBy revealing two distinct logical types of control, our approach provides basic insights into both the organizational principles of transcriptional regulation and the mechanisms buffering genetic flexibility. We anticipate that the general concept of distinguishing logical types of control will apply to many complex biological networks.

Highlights

IntroductionTranscriptional responses to alterations of DNA superhelicity reveal non-trivial spatial patterns, raising new questions on the coordination of genomic transcription [9,11] and the interplay between chromosomal organization and patterns in gene expression is becoming the focus of computational analyses [12,13]
In the bacterium Escherichia coli the transcriptional regulation of gene expression involves both dedicated regulators binding specific DNA sites with high affinity and global regulators – abundant DNA architectural proteins of the bacterial nucleoid binding multiple sites with a wide range of affinities and modulating the superhelical density of DNA
Here we look at the properties of effective networks derived from significant gene expression changes under variation of the two forms of control and find that upon limitations of one type of control the other type can compensate for compromised regulation

Summary

Introduction

Transcriptional responses to alterations of DNA superhelicity reveal non-trivial spatial patterns, raising new questions on the coordination of genomic transcription [9,11] and the interplay between chromosomal organization and patterns in gene expression is becoming the focus of computational analyses [12,13] From these considerations it is obvious that a holistic theory of transcriptional regulation has to include the relationships between these two logically distinct (digitalbinary and analog-continuous) types of information and has to distinguish them in the first place. Other mechanisms of gene regulation between the binary and continuous extremes can be considered, for understanding the organizational principles of transcriptional regulation we assume a working model here in which the impacts of the two distinct logical types of control – one of digital and another of analog type – are to be clearly distinguished and related to each other

Methods

Results

Discussion

Conclusion