Composition of Transcription Machinery and Its Crosstalk with Nucleoid-Associated Proteins and Global Transcription Factors

Abstract

The coordination of bacterial genomic transcription involves an intricate network of interdependent genes encoding nucleoid-associated proteins (NAPs), DNA topoisomerases, RNA polymerase subunits and modulators of transcription machinery. The central element of this homeostatic regulatory system, integrating the information on cellular physiological state and producing a corresponding transcriptional response, is the multi-subunit RNA polymerase (RNAP) holoenzyme. In this review article, we argue that recent observations revealing DNA topoisomerases and metabolic enzymes associated with RNAP supramolecular complex support the notion of structural coupling between transcription machinery, DNA topology and cellular metabolism as a fundamental device coordinating the spatiotemporal genomic transcription. We analyse the impacts of various combinations of RNAP holoenzymes and global transcriptional regulators such as abundant NAPs, on genomic transcription from this viewpoint, monitoring the spatiotemporal patterns of couplons—overlapping subsets of the regulons of NAPs and RNAP sigma factors. We show that the temporal expression of regulons is by and large, correlated with that of cognate regulatory genes, whereas both the spatial organization and temporal expression of couplons is distinctly impacted by the regulons of NAPs and sigma factors. We propose that the coordination of the growth phase-dependent concentration gradients of global regulators with chromosome configurational dynamics determines the spatiotemporal patterns of genomic expression.

The economy of chromosomal distances in bacterial gene regulation

“…When high-resolution single-cell data of chromosome structure and chromosome dynamics will become available, one can start exploring these questions beyond the circle approximation employed here, in order to study the interplay of chromosomal dynamics and TF-based gene regulation in further detail 45 , 46 .…”

Spatiotemporal Coupling of DNA Supercoiling and Genomic Sequence Organization—A Timing Chain for the Bacterial Growth Cycle?

“…The dynamic constraints of DNA supercoils by NAPs are, by and large, responsible for rendering the chromosome structure and gene expression interdependent. Both the abundance and composition of NAPs vary continuously forming temporal concentration gradients during the growth cycle [ 34 , 35 , 36 ], whereas their expression is in turn, regulated by ppGpp and/or by DNA supercoiling [ 1 , 37 , 38 , 39 , 40 , 41 , 42 ]. DNA supercoiling modulates not only the gene expression but also the efficiency of DNA binding by NAPs [ 43 , 44 , 45 , 46 ], whereas ppGpp can modulate the NAP-binding effect by protein modification [ 47 ].…”

“…Intrinsically curved DNA sequences were shown to facilitate the pinning of plectonemic supercoils upstream of the promoter [ 81 ]. Furthermore, the variations in canonical promoter elements such as the G/C content of the discriminator sequence (the sequence between the −10 hexamer and the transcription start site) and the length of the spacer between the −10 and −35 hexamers, were shown to be determinative for the promoter supercoiling response [ 40 , 42 , 82 , 83 , 84 , 85 , 86 ]. For example, the “stringent” promoters (such as stable RNA promoters) that are, respectively, down- and up-regulated by ppGpp and negative supercoiling are characterized by G/C-rich discriminators, short (16 bp) spacers, and suboptimal −35 hexamers as well as anisotropically bendable upstream activating sequences (UAS) forming coherently bent DNA microloops associated with RNAP [ 55 , 87 , 88 ].…”

“…For example, the “stringent” promoters (such as stable RNA promoters) that are, respectively, down- and up-regulated by ppGpp and negative supercoiling are characterized by G/C-rich discriminators, short (16 bp) spacers, and suboptimal −35 hexamers as well as anisotropically bendable upstream activating sequences (UAS) forming coherently bent DNA microloops associated with RNAP [ 55 , 87 , 88 ]. Overall, the more A/T-rich and more G/C-rich sequences are associated with a response to low and high levels of negative superhelicity, respectively [ 42 , 84 , 85 ].…”

Chromosomal position of ribosomal protein genes impacts long term evolution ofVibrio cholerae

“…The genomic position of key gene groups is widely conserved along the ori-ter axis following the temporal pattern of gene expression (17, 18, 21, 22). Thus, coding sequences expressed in exponential phase are physically associated to the oriC region while factors transcribed in stress situations or in stationary phase cluster close to the ter region (17, 21, 23–26). Consistently, it was recently shown that some genes need a specific genomic location to achieve their function (16).…”