scholarly journals Competition between binding sites determines gene expression at low transcription factor concentrations

2015 ◽  
Author(s):  
David van Dijk ◽  
Eilon Sharon ◽  
Maya Lotan-Pompan ◽  
Adina Weinberger ◽  
Eran Segal ◽  
...  

AbstractThe response of gene expression to intra-and extra-cellular cues is largely mediated through changes in the activity of transcription factors (TFs), whose sequence specificities are largely known. However, the rules by which promoters decode the amount of active TF into gene expression are not well understood. Here, we measure the activity of 6500 designed promoters at six different levels of TF activity in budding yeast. We observe that maximum promoter activity is determined by TF activity and not by the number of sites. Surprisingly, the addition of an activator-binding site often reduces expression. A thermodynamic model that incorporates competition between neighboring binding sites for a local pool of TF molecules explains this behavior and accurately predicts both absolute expression and the amount by which addition of a site increases or reduces expression. Taken together, our findings support a model in which neighboring binding sites interact competitively when TF is limiting but otherwise act additivelySignificance StatementIn response to intracellular and extracellular signals organisms alter the concentration and activity of transcription factors (TFs), proteins that regulate gene expression. However, the molecular mechanisms that determine the response of a target promoter to changes in the number of active TF molecules are not well understood. By combining mathematical modeling with measurements of TF dose-response curves for thousands of designed promoters, we show that competition for active TF molecules is a major factor in determining gene expression. At low TF concentrations additional activator-binding sites within a promoter can actually reduce expression. Thermodynamic modeling suggests that steric hindrance between neighboring binding sites cannot explain this behavior, but that competition for limiting TF molecules can.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Nan Deng ◽  
Chen Hou ◽  
Boxiang He ◽  
Fengfeng Ma ◽  
Qingan Song ◽  
...  

Abstract Background Gnetum is an economically important tropical and subtropical gymnosperm genus with various dietary, industrial and medicinal uses. Many carbohydrates, proteins and fibers accumulate during the ripening of Gnetum seeds. However, the molecular mechanisms related to this process remain unknown. Results We therefore assembled a full-length transcriptome from immature and mature G. luofuense seeds using PacBio sequencing reads. We identified a total of 5726 novel genes, 9061 alternative splicing events, 3551 lncRNAs, 2160 transcription factors, and we found that 8512 genes possessed at least one poly(A) site. In addition, gene expression comparisons of six transcriptomes generated by Illumina sequencing showed that 14,323 genes were differentially expressed from an immature stage to a mature stage with 7891 genes upregulated and 6432 genes downregulated. The expression of 14 differentially expressed transcription factors from the MADS-box, Aux/IAA and bHLH families was validated by qRT-PCR, suggesting that they may have important roles in seed ripening of G. luofuense. Conclusions These findings provide a valuable molecular resource for understanding seed development of gymnosperms.


2020 ◽  
Author(s):  
Nan deng ◽  
Chen Hou ◽  
Boxiang He ◽  
Fengfeng Ma ◽  
Qingan Song ◽  
...  

Abstract Background: Gnetum is an economically important tropical and subtropical gymnosperm genus with various dietary, industrial and medicinal uses. Many carbohydrates, proteins and fibers accumulate during the ripening of Gnetum seeds. However, the molecular mechanisms related to this process remain unknown.Results: We therefore assembled a full-length transcriptome from immature and mature G. luofuense seeds using PacBio sequencing reads. We identified a total of 5,726 novel genes, 9,061 alternative splicing events, 3,551 lncRNAs, 2,160 transcription factors, and we found that 8,512 genes possessed at least one poly(A) site. In addition, gene expression comparisons of six transcriptomes generated by Illumina sequencing showed that 14,323 genes were differentially expressed from an immature stage to a mature stage with 7,891 genes upregulated and 6,432 genes downregulated. The expression of 14 differentially expressed transcription factors from the MADS-box, Aux/IAA and bHLH families was validated by qRT-PCR, suggesting that they may have important roles in seed ripening of G. luofuense.Conclusions: These findings provide a valuable molecular resource for understanding seed development of gymnosperms.


2020 ◽  
Author(s):  
Nan deng ◽  
Chen Hou ◽  
Boxiang He ◽  
Fengfeng Ma ◽  
Qingan Song ◽  
...  

Abstract Background: Gnetum is an economically important tropical and subtropical gymnosperm genus with various dietary, industrial and medicinal uses. Many carbohydrates, proteins and secondary metabolic compounds accumulate during the ripening of Gnetum seeds.However, the molecular mechanisms related to this process remain unknown. Results: We therefore assembled a full-length transcriptome from immature and mature G. luofuenseseeds using PacBio sequencingreads. We identified a total of 5,726 novel genes, 9,061 alternative splicing events, 3,551 lncRNAs, 2,160 transcription factors, and 359 fusion genes, and we found that 8,512 genes possessed at least one poly(A) site. In addition, gene expression comparisons of six transcriptomes generated by Illumina sequencing showed that14,323 genes were differentially expressed from an immature stage to a mature stage with 7,891 genes upregulated and 6,432 genes downregulated. The expression of 14 differentially expressed transcription factors from the MADS-box, Aux/IAA and bHLH families was validated by qRT-PCR, suggesting that they may have important roles in seed ripening of G. luofuense. Conclusions:These findings provide a valuable molecular resource for domestication and cultivation of Gnetum species.


2020 ◽  
Author(s):  
Nan deng ◽  
Chen Hou ◽  
Boxiang He ◽  
Fengfeng Ma ◽  
Qingan Song ◽  
...  

Abstract Background: Gnetum is an economically important tropical and subtropical gymnosperm genus with various dietary, industrial and medicinal uses. Many carbohydrates, proteins and fibers accumulate during the ripening of Gnetum seeds. However, the molecular mechanisms related to this process remain unknown.Results: We therefore assembled a full-length transcriptome from immature and mature G. luofuense seeds using PacBio sequencing reads. We identified a total of 5,726 novel genes, 9,061 alternative splicing events, 3,551 lncRNAs, 2,160 transcription factors, and we found that 8,512 genes possessed at least one poly(A) site. In addition, gene expression comparisons of six transcriptomes generated by Illumina sequencing showed that 14,323 genes were differentially expressed from an immature stage to a mature stage with 7,891 genes upregulated and 6,432 genes downregulated. The expression of 14 differentially expressed transcription factors from the MADS-box, Aux/IAA and bHLH families was validated by qRT-PCR, suggesting that they may have important roles in seed ripening of G. luofuense.Conclusions: These findings provide a valuable molecular resource for understanding seed development of gymnosperms.


2019 ◽  
Vol 70 (19) ◽  
pp. 5355-5374 ◽  
Author(s):  
Dandan Zang ◽  
Jingxin Wang ◽  
Xin Zhang ◽  
Zhujun Liu ◽  
Yucheng Wang

Abstract Plant heat shock transcription factors (HSFs) are involved in heat and other abiotic stress responses. However, their functions in salt tolerance are little known. In this study, we characterized the function of a HSF from Arabidopsis, AtHSFA7b, in salt tolerance. AtHSFA7b is a nuclear protein with transactivation activity. ChIP-seq combined with an RNA-seq assay indicated that AtHSFA7b preferentially binds to a novel cis-acting element, termed the E-box-like motif, to regulate gene expression; it also binds to the heat shock element motif. Under salt conditions, AtHSFA7b regulates its target genes to mediate serial physiological changes, including maintaining cellular ion homeostasis, reducing water loss rate, decreasing reactive oxygen species accumulation, and adjusting osmotic potential, which ultimately leads to improved salt tolerance. Additionally, most cellulose synthase-like (CSL) and cellulose synthase (CESA) family genes were inhibited by AtHSFA7b; some of them were randomly selected for salt tolerance characterization, and they were mainly found to negatively modulate salt tolerance. By contrast, some transcription factors (TFs) were induced by AtHSFA7b; among them, we randomly identified six TFs that positively regulate salt tolerance. Thus, AtHSFA7b serves as a transactivator that positively mediates salinity tolerance mainly through binding to the E-box-like motif to regulate gene expression.


2018 ◽  
Author(s):  
Ashley M. Ingiosi ◽  
Taylor Wintler ◽  
Hannah Schoch ◽  
Kristan G. Singletary ◽  
Dario Righelli ◽  
...  

AbstractAutism Spectrum Disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States and often co-presents with sleep problems. Sleep problems in ASD predict the severity of ASD core diagnostic symptoms and have a considerable impact on the quality of life of caregivers. Little is known, however, about the underlying molecular mechanisms. We investigated the role of Shank3, a high confidence ASD gene candidate, in sleep architecture and regulation. We show that mice lacking exon 21 of Shank3 have problems falling asleep even when sleepy. Using RNA-seq we show that sleep deprivation increases the differences in gene expression between mutants and wild types, downregulating circadian transcription factors Per3, Dec2, Hlf, Tef, and Reverbα. Shank3 mutants also have trouble regulating wheel-running activity in constant darkness. Overall our study shows that Shank3 is an important modulator of sleep and clock gene expression.


Author(s):  
Steven E. Hyman ◽  
Eric J. Nestler

This chapter provides an overview of the fundamental molecular processes by which information is encoded in the genome and how this information is expressed within an environmental context. We describe what genes are, how they function, and how their expression into RNA and protein is regulated by signals from outside the cell. Particular attention is given to a series of stimulus-regulated transcription factors, which play important roles in transducing information from the cell surface to the nucleus. Work in this area has shown that the control of gene expression by extracellular signals is a critical arena for gene–environment interactions that are highly relevant to psychiatry.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Saivageethi Nuthikattu ◽  
Dragan Milenkovic ◽  
John Rutledge ◽  
Amparo Villablanca

AbstractHyperlipidemia is a risk factor for dementia, and chronic consumption of a Western Diet (WD) is associated with cognitive impairment. However, the molecular mechanisms underlying the development of microvascular disease in the memory centers of the brain are poorly understood. This pilot study investigated the nutrigenomic pathways by which the WD regulates gene expression in hippocampal brain microvessels of female mice. Five-week-old female low-density lipoprotein receptor deficient (LDL-R−/−) and C57BL/6J wild type (WT) mice were fed a chow or WD for 8 weeks. Metabolics for lipids, glucose and insulin were determined. Differential gene expression, gene networks and pathways, transcription factors, and non-protein coding RNAs were evaluated by genome-wide microarray and bioinformatics analysis of laser captured hippocampal microvessels. The WD resulted in differential expression of 2,412 genes. The majority of differential gene expression was attributable to differential regulation of cell signaling proteins and their transcription factors, approximately 7% was attributable to differential expression of miRNAs, and a lesser proportion was due to other non-protein coding RNAs, primarily long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs) not previously described to be modified by the WD in females. Our findings revealed that chronic consumption of the WD resulted in integrated multilevel molecular regulation of the hippocampal microvasculature of female mice and may provide one of the mechanisms underlying vascular dementia.


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