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. 2015 Mar 19;10(3):e0120848.
doi: 10.1371/journal.pone.0120848. eCollection 2015.

Functional analysis of the molecular interactions of TATA box-containing genes and essential genes

Sang-Hun Bae  1 , Hyun Wook Han  1 , Jisook Moon  1
Affiliations

Functional analysis of the molecular interactions of TATA box-containing genes and essential genes

Sang-Hun Bae et al. PLoS One. .

Abstract

Genes can be divided into TATA-containing genes and TATA-less genes according to the presence of TATA box elements at promoter regions. TATA-containing genes tend to be stress-responsive, whereas many TATA-less genes are known to be related to cell growth or "housekeeping" functions. In a previous study, we demonstrated that there are striking differences among four gene sets defined by the presence of TATA box (TATA-containing) and essentiality (TATA-less) with respect to number of associated transcription factors, amino acid usage, and functional annotation. Extending this research in yeast, we identified KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways that are statistically enriched in TATA-containing or TATA-less genes and evaluated the possibility that the enriched pathways are related to stress or growth as reflected by the individual functions of the genes involved. According to their enrichment for either of these two gene sets, we sorted KEGG pathways into TATA-containing-gene-enriched pathways (TEPs) and essential-gene-enriched pathways (EEPs). As expected, genes in TEPs and EEPs exhibited opposite results in terms of functional category, transcriptional regulation, codon adaptation index, and network properties, suggesting the possibility that the bipolar patterns in these pathways also contribute to the regulation of the stress response and to cell survival. Our findings provide the novel insight that significant enrichment of TATA-binding or TATA-less genes defines pathways as stress-responsive or growth-related.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Classification of KEGG pathways into essential-gene-enriched pathways (EEPs) and TATA-containing-gene-enriched pathways (TEPs).
(a) We created a network to show which KEGG pathway (ellipse node) belongs to EEPs or TEPs (round rectangle nodes) and which one is included in metabolic pathways (diamond node in the center). The relations are described as edges between two nodes; for instance, glycolysis belongs to TEPs and metabolic pathways. Color (upper-right) represents an adjusted p-value in enrichment analysis. (b) The bar graph shows the results of GO (gene ontology) enrichment analysis in EEPs and TEPs. The red dashed lines correspond to the log transformation of an adjusted p-value of 0.05. BP, biological process; MF, molecular function.
Fig 2
Fig 2. Marked differences in genes and pathways between EEPs and TEPs.
(a) The heat map of the adjusted p-values obtained from the enrichment test showed that EEPs are obviously different from TEPs. Rows represent genes and columns pathways (pathway ID); colors represent the negative log transformation of the adjusted p-values, showing the extent to which essential and TATA genes are enriched in the corresponding pathways. (b) Essential-gene-enriched pathways (EEPs) and (c) TATA-containing-gene-enriched pathways (TEPs). The enriched pathways were sorted according to the negative log of the adjusted p-value. The red dashed lines correspond to the log transformation of an adjusted p-value of 0.05.
Fig 3
Fig 3. Functional comparison of EEPs and TEPs.
(a) Genes of TEPs tend to be associated with a greater number of transcription factors than EEPs. (b) The transcription of TEPs is preferentially associated with the SAGA complex, a regulator of transcription that is known to be related to the stress response. The red dashed lines correspond to the negative log transformation of an adjusted p-value of 0.05. (c) Most TEPs exhibit a higher CAI (codon adaptation index) compared with the EEPs.
Fig 4
Fig 4. Degrees and connectivity in the interaction network.
(a) The mean degrees of molecular interactions are significantly higher (p<0.05) in genes of EEPs than in genes of TEPs. (b) Genes of EEPs were over-represented for higher-scored or highly interconnected clusters, whereas those of TEPs were over-represented for less-scored clusters. The X-axis represents clusters that are displayed in the order of the scores, with the cluster in the left corner having the highest scores.
Fig 5
Fig 5. Comparison of pathways in TEPs and EEPs on metabolic map.
(a) TEPs and (b) EEPs are associated with different modules in the metabolic pathways analysis; these are highlighted in color (red for TEPs and blue for EEPs). Most of the TEPs in the metabolic pathways are associated with carbohydrate metabolism. Circles indicate compounds in the metabolic pathways.
Fig 6
Fig 6. Enrichment of metabolic pathways and enzyme.
(a) There is a marked difference in the enriched metabolic pathways between TATA and essential genes. (b) Oxidoreductases are enriched in the enzyme set (197 enzymes) of the TEPs, whereas transferases are enriched in the enzyme set (124) of the EEPs. The red dashed lines correspond to the negative log transformation of an adjusted p-value of 0.05.
Fig 7
Fig 7. Representative pathways in TEPs and EEPs.
(a) Glycolysis is the top-ranked pathway of TEPs. (b) Ribosome biogenesis is the top-ranked pathway of EEPs. Nodes that are highlighted in blue contain at least one essential gene; nodes highlighted in red contain at least one TATA-containing gene. Color intensity is proportional to the number of corresponding genes.
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This work was supported by Ministry of health and welfare, A120300, http://english.mw.go.kr/front_eng/index.jsp (JM), and Korea Science and Engineering Foundation, 2011-0013280, www.nrf.re.kr (JM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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