A computational study of bacterial gene regulation and adaptation ...
A computational study of bacterial gene regulation and adaptation ...
A computational study of bacterial gene regulation and adaptation ...
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metabolism / carbon nutrition with development. This is potentially due to CRP, which isindirectly controlled by glucose availability <strong>and</strong> is a top-level regulator <strong>of</strong> both sugarmetabolism <strong>and</strong> these developmental processes. A second control point integrating these tw<strong>of</strong>unctions operates at a post-transcriptional level. CsrA <strong>and</strong> CsrB - an mRNA-binding protein<strong>and</strong> a small RNA that interrupts this binding - are known to control diverse processesincluding gluconeo<strong>gene</strong>sis <strong>and</strong> motility / bi<strong>of</strong>ilm formation (Romeo 1998). Thus, thoughcertain aspects <strong>of</strong> two functional modules - metabolism <strong>and</strong> developmental processes - maybe inseparable, additional control mechanisms may be operating in developmental processesthus establishing tighter control.Even within metabolism, three broad functions - catabolism, anabolism <strong>and</strong> centralmetabolism - can be defined. These differ from each other in the number <strong>and</strong> types <strong>of</strong>regulators they come under (Seshasayee et al. 2009). Due to the effect <strong>of</strong> CRP, most catabolic<strong>gene</strong>s come under the control <strong>of</strong> more than one TF, <strong>and</strong> in <strong>gene</strong>ral, a combination <strong>of</strong> a global<strong>and</strong> a local TF. Exceptions are known: for example, the lac operon is regulated by CRP <strong>and</strong>LacI, but does not involve an FFL. Despite the similarity in network architectures, differentsugar operons display different output patterns in response to input signals. On the other h<strong>and</strong>,anabolic <strong>gene</strong>s are regulated by a single TF each, which has been interpreted as leading to thephenomenon <strong>of</strong> ‘just-in-time transcription’. Thirdly, central metabolism, which is the endpoint<strong>of</strong> most catabolic pathways <strong>and</strong> produces precursor molecules for most <strong>of</strong> anabolism, iscontrolled by a multitude <strong>of</strong> global TFs.In total, these studies have shown that different categories <strong>of</strong> <strong>gene</strong>s come under the control <strong>of</strong>different transcriptional regulatory architectures in a manner that is consistent with functionalexpectations.I.4.4. Constraints on genomic organisation imposed by transcriptional<strong>regulation</strong>A key mechanistic question in transcriptional <strong>regulation</strong> is how a TF finds its target site.Mechanisms that combine 3D diffusion in the cellular volume <strong>and</strong> 1D tracking along theDNA have been proposed (Kolesov et al. 2007). Various groups have attempted to answerhow genomic organisation is in fact governed by transcriptional <strong>regulation</strong>, the first evidence15
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