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Coordination logic of the sensing machinery in the transcriptional regulatory network of Escherichia coli.

Janga SC, Salgado H, Martínez-Antonio A, Collado-Vides J - Nucleic Acids Res. (2007)

Bottom Line: The active and inactive state of transcription factors in growing cells is usually directed by allosteric physicochemical signals or metabolites, which are in turn either produced in the cell or obtained from the environment by the activity of the products of effector genes.Finally we show that evolutionary families of TFs do not show a tendency to preserve their sensing abilities.Our results provide a detailed panorama of the topological structures of E. coli TRN and the way TFs they compose off, sense their surroundings by coordinating responses.

View Article: PubMed Central - PubMed

Affiliation: Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, 62100, México. sarath@ccg.unam.mx

ABSTRACT
The active and inactive state of transcription factors in growing cells is usually directed by allosteric physicochemical signals or metabolites, which are in turn either produced in the cell or obtained from the environment by the activity of the products of effector genes. To understand the regulatory dynamics and to improve our knowledge about how transcription factors (TFs) respond to endogenous and exogenous signals in the bacterial model, Escherichia coli, we previously proposed to classify TFs into external, internal and hybrid sensing classes depending on the source of their allosteric or equivalent metabolite. Here we analyze how a cell uses its topological structures in the context of sensing machinery and show that, while feed forward loops (FFLs) tightly integrate internal and external sensing TFs connecting TFs from different layers of the hierarchical transcriptional regulatory network (TRN), bifan motifs frequently connect TFs belonging to the same sensing class and could act as a bridge between TFs originating from the same level in the hierarchy. We observe that modules identified in the regulatory network of E. coli are heterogeneous in sensing context with a clear combination of internal and external sensing categories depending on the physiological role played by the module. We also note that propensity of two-component response regulators increases at promoters, as the number of TFs regulating a target operon increases. Finally we show that evolutionary families of TFs do not show a tendency to preserve their sensing abilities. Our results provide a detailed panorama of the topological structures of E. coli TRN and the way TFs they compose off, sense their surroundings by coordinating responses.

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Distribution of different sensing categories seen in 13 evolutionary families of transcription factors. Only those families in which atleast two of the transcription factors could be associated with a sensing class are shown. (a) Heatmap showing the fraction of TFs in a given family belonging to different sensing classes. A dark red corresponds to 1.0 while a black color cell represents no TF associated to a class. Families and sensing classes are clustered hierarchically to view similarities in distributions. (b) Histogram showing the proportion of different sensing classes in each evolutionary family calculated against the total number of TFs of a family assigned to sensing classes. Certain families like IclR, AsnC, TetR were found to contain only two TFs which could be associated to sensing classes, while LacI, LuxR, AraC and GntR comprised of 11, 9, 8 and 7 TFs, respectively. The number of TFs in all other families was between 2 and 6.
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Figure 6: Distribution of different sensing categories seen in 13 evolutionary families of transcription factors. Only those families in which atleast two of the transcription factors could be associated with a sensing class are shown. (a) Heatmap showing the fraction of TFs in a given family belonging to different sensing classes. A dark red corresponds to 1.0 while a black color cell represents no TF associated to a class. Families and sensing classes are clustered hierarchically to view similarities in distributions. (b) Histogram showing the proportion of different sensing classes in each evolutionary family calculated against the total number of TFs of a family assigned to sensing classes. Certain families like IclR, AsnC, TetR were found to contain only two TFs which could be associated to sensing classes, while LacI, LuxR, AraC and GntR comprised of 11, 9, 8 and 7 TFs, respectively. The number of TFs in all other families was between 2 and 6.

Mentions: Most prokaryotic TFs are multi-domain proteins, typically composed of a DNA-binding domain along with a signaling small molecule-binding domain. Since the majority of the bacterial TFs can be classified into evolutionary families based on their helix–turn–helix DNA-binding domain, we identified a total of 13 evolutionary families of TFs for which sensing classes could be assigned (see Materials and Methods section). One could expect that TFs belonging to a common evolutionary family might be composed of the same sensing class as they might have evolved from a common DNA-binding domain. However, as can be seen from Figure 6, this does not appear to be the case. Most families which contain at least three TFs are composed of an extensive mix of TFs from different sensing classes indicating that TFs of the same evolutionary family need not belong to the same class of sensing. For example, four major families LacI, LuxR, AraC and GntR in this figure do not clearly show enrichment for one or the other kind of sensing category. These observations can be explained under the premise that the sensing class of a TF could actually depend on its signaling domain rather than its DNA-binding domain and hence, although two TFs can belong to the same evolutionary family they could still correspond to different classes as their ability to respond to the signals will depend on their signaling domain. In addition, it is now well accepted that there are extensive variations and frequent recombinations and rearrangements occurring in the signaling domains of TFs having the same DNA-binding domain, suggesting that unless TFs of an evolutionary family are recent duplicates, in which case they might conserve their signaling domain, it is unlikely that they still preserve their sensing mechanism (23,24,40). It can also be seen from the hierarchical clustering of sensing classes in Figure 6a that the majority of the TF families show a tendency to come from one of the following two combinations of sensing classes: ISM and H appearing with ETM or IDB appearing with ETC in a given family. This suggests a higher order relationship in the evolution of sensing mechanisms in TFs—the former indicating a link among those sensing endogenous and endogenous metabolites and the later linking nucleoid-associated TFs with two-component systems.Figure 6.


Coordination logic of the sensing machinery in the transcriptional regulatory network of Escherichia coli.

Janga SC, Salgado H, Martínez-Antonio A, Collado-Vides J - Nucleic Acids Res. (2007)

Distribution of different sensing categories seen in 13 evolutionary families of transcription factors. Only those families in which atleast two of the transcription factors could be associated with a sensing class are shown. (a) Heatmap showing the fraction of TFs in a given family belonging to different sensing classes. A dark red corresponds to 1.0 while a black color cell represents no TF associated to a class. Families and sensing classes are clustered hierarchically to view similarities in distributions. (b) Histogram showing the proportion of different sensing classes in each evolutionary family calculated against the total number of TFs of a family assigned to sensing classes. Certain families like IclR, AsnC, TetR were found to contain only two TFs which could be associated to sensing classes, while LacI, LuxR, AraC and GntR comprised of 11, 9, 8 and 7 TFs, respectively. The number of TFs in all other families was between 2 and 6.
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Figure 6: Distribution of different sensing categories seen in 13 evolutionary families of transcription factors. Only those families in which atleast two of the transcription factors could be associated with a sensing class are shown. (a) Heatmap showing the fraction of TFs in a given family belonging to different sensing classes. A dark red corresponds to 1.0 while a black color cell represents no TF associated to a class. Families and sensing classes are clustered hierarchically to view similarities in distributions. (b) Histogram showing the proportion of different sensing classes in each evolutionary family calculated against the total number of TFs of a family assigned to sensing classes. Certain families like IclR, AsnC, TetR were found to contain only two TFs which could be associated to sensing classes, while LacI, LuxR, AraC and GntR comprised of 11, 9, 8 and 7 TFs, respectively. The number of TFs in all other families was between 2 and 6.
Mentions: Most prokaryotic TFs are multi-domain proteins, typically composed of a DNA-binding domain along with a signaling small molecule-binding domain. Since the majority of the bacterial TFs can be classified into evolutionary families based on their helix–turn–helix DNA-binding domain, we identified a total of 13 evolutionary families of TFs for which sensing classes could be assigned (see Materials and Methods section). One could expect that TFs belonging to a common evolutionary family might be composed of the same sensing class as they might have evolved from a common DNA-binding domain. However, as can be seen from Figure 6, this does not appear to be the case. Most families which contain at least three TFs are composed of an extensive mix of TFs from different sensing classes indicating that TFs of the same evolutionary family need not belong to the same class of sensing. For example, four major families LacI, LuxR, AraC and GntR in this figure do not clearly show enrichment for one or the other kind of sensing category. These observations can be explained under the premise that the sensing class of a TF could actually depend on its signaling domain rather than its DNA-binding domain and hence, although two TFs can belong to the same evolutionary family they could still correspond to different classes as their ability to respond to the signals will depend on their signaling domain. In addition, it is now well accepted that there are extensive variations and frequent recombinations and rearrangements occurring in the signaling domains of TFs having the same DNA-binding domain, suggesting that unless TFs of an evolutionary family are recent duplicates, in which case they might conserve their signaling domain, it is unlikely that they still preserve their sensing mechanism (23,24,40). It can also be seen from the hierarchical clustering of sensing classes in Figure 6a that the majority of the TF families show a tendency to come from one of the following two combinations of sensing classes: ISM and H appearing with ETM or IDB appearing with ETC in a given family. This suggests a higher order relationship in the evolution of sensing mechanisms in TFs—the former indicating a link among those sensing endogenous and endogenous metabolites and the later linking nucleoid-associated TFs with two-component systems.Figure 6.

Bottom Line: The active and inactive state of transcription factors in growing cells is usually directed by allosteric physicochemical signals or metabolites, which are in turn either produced in the cell or obtained from the environment by the activity of the products of effector genes.Finally we show that evolutionary families of TFs do not show a tendency to preserve their sensing abilities.Our results provide a detailed panorama of the topological structures of E. coli TRN and the way TFs they compose off, sense their surroundings by coordinating responses.

View Article: PubMed Central - PubMed

Affiliation: Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, 62100, México. sarath@ccg.unam.mx

ABSTRACT
The active and inactive state of transcription factors in growing cells is usually directed by allosteric physicochemical signals or metabolites, which are in turn either produced in the cell or obtained from the environment by the activity of the products of effector genes. To understand the regulatory dynamics and to improve our knowledge about how transcription factors (TFs) respond to endogenous and exogenous signals in the bacterial model, Escherichia coli, we previously proposed to classify TFs into external, internal and hybrid sensing classes depending on the source of their allosteric or equivalent metabolite. Here we analyze how a cell uses its topological structures in the context of sensing machinery and show that, while feed forward loops (FFLs) tightly integrate internal and external sensing TFs connecting TFs from different layers of the hierarchical transcriptional regulatory network (TRN), bifan motifs frequently connect TFs belonging to the same sensing class and could act as a bridge between TFs originating from the same level in the hierarchy. We observe that modules identified in the regulatory network of E. coli are heterogeneous in sensing context with a clear combination of internal and external sensing categories depending on the physiological role played by the module. We also note that propensity of two-component response regulators increases at promoters, as the number of TFs regulating a target operon increases. Finally we show that evolutionary families of TFs do not show a tendency to preserve their sensing abilities. Our results provide a detailed panorama of the topological structures of E. coli TRN and the way TFs they compose off, sense their surroundings by coordinating responses.

Show MeSH
Related in: MedlinePlus