From sequence to dynamics: the effects of transcription factor and polymerase concentration changes on activated and repressed promoters

By Abel D González Pérez, Vladimir Espinosa Angarica, Julio Collado-Vides, A. T. R. Vasconcelos. BMC Molecular Biology, 2009

631 citations recorded by the source corpus.

BackgroundThe fine tuning of two features of the bacterial regulatory machinery have been known to contribute to the diversity of gene expression within the same regulon: the sequence of Transcription Factor (TF) binding sites, and their location with respect to promoters. While variations of binding sequences modulate the strength of the interaction between the TF and its binding sites, the distance between binding sites and promoters alter the interaction between the TF and the RNA polymerase (RNAP).ResultsIn this paper we estimated the dissociation constants (Kd) of several E. coli TFs in their interaction with variants of their binding sequences from the scores resulting from aligning them to Positional Weight Matrices. A correlation coefficient of 0.78 was obtained when pooling together sites for different TFs. The theoretically estimated Kdvalues were then used, together with the dissociation constants of the RNAP-promoter interaction to analyze activated and repressed promoters. The strength of repressor sites -- i.e., the strength of the interaction between TFs and their binding sites -- is slightly higher than that of activated sites. We explored how different factors such as the variation of binding sequences, the occurrence of more than one binding site, or different RNAP concentrations may influence the promoters' response to the variations of TF concentrations. We found that the occurrence of several regulatory sites bound by the same TF close to a promoter -- if they are bound by the TF in an independent manner -- changes the effect of TF concentrations on promoter occupancy, with respect to individual sites. We also found that the occupancy of a promoter will never be more than half if the RNAP concentration-to-Kpratio is 1 and the promoter is subject to repression; or less than half if the promoter is subject to activation. If the ratio falls to 0.1, the upper limit of occupancy probability for repressed drops below 10%; a descent of the limits occurs also for activated promoters.ConclusionThe number of regulatory sites may thus act as a versatility-producing device, in addition to serving as a source of robustness of the transcription machinery. Furthermore, our results show that the effects of TF concentration fluctuations on promoter occupancy are constrained by RNAP concentrations.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/13cfc05e30bd3df330756e95d8547f8d24e01e37

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In Genetics

1. Bartłomiej Kozera
2. M. Migocka
3. A. Papierniak
4. Marcin Rapacz

In Molecular Biology

1. Bartłomiej Kozera
2. M. Migocka
3. A. Papierniak
4. Marcin Rapacz

Citations in the corpus

• Reference genes in real-time PCR (2013, background): “…as reference for example for rice cultivars (Kim et al. 2003) and potato (Nicot et al. 2005) while going further in time (as it seems) it was generally not recommended for plants like peach (Tong et al. 2009), rice (Li et al. 2010), cucumber (Wan et al. 2010) or papaya (Zhu et al. 2012).”
• Identification of suitable reference genes for studying gene expression in cucumber plants subjected to abiotic stress and growth regulators (2011, background): “It had been previously proved that the expression of CYP varied in different tissue samples of peach, in tomato subjected to different biotic and abiotic stress, and in grapevine throughout berry development (Nicot et al. 2005; Reid et al. 2006; Tong et al. 2009).”