Nucleosomal Context of Binding Sites Influences Transcription Factor Binding Affinity and Gene Regulation

Transcription factor (TF) binding to its DNA target site plays an essential role in gene regulation. The location, orientation and spacing of transcription factor binding sites (TFBSs) also affect regulatory function of the TF. However, how nucleosomal context of TFBSs influences TF binding and subsequent gene regulation remains to be elucidated. Using genome-wide nucleosome positioning and TF binding data in budding yeast, we found that binding affinities of TFs to DNA tend to decrease with increasing nucleosome occupancy of the associated binding sites. We further demonstrated that nucleosomal context of binding sites is correlated with gene regulation of the corresponding TF. Nucleosome-depleted TFBSs are linked to high gene activity and low expression noise, whereas nucleosome-covered TFBSs are associated with low gene activity and high expression noise. Moreover, nucleosome-covered TFBSs tend to disrupt coexpression of the corresponding TF target genes. We conclude that nucleosomal context of binding sites influences TF binding affinity, subsequently affecting the regulation of TFs on their target genes. This emphasizes the need to include nucleosomal context of TFBSs in modeling gene regulation

Robustness of transcriptional regulatory program influences gene expression variability

<p>Abstract</p> <p>Background</p> <p>Most genes are not affected when any transcription factor (TF) is knocked out, indicating that they have robust transcriptional regulatory program. Yet the mechanism underlying robust transcriptional regulatory program is less clear.</p> <p>Results</p> <p>Here, we studied the cause and effect of robust transcriptional regulatory program. We found that cooperative TFs in the robust transcriptional regulatory program regulate their common target genes in an activity-redundant fashion, and they are able to compensate for each other's loss. As a result, their target genes are insensitive to their single perturbation. We next revealed that the degree of robustness of transcriptional regulatory program influences gene expression variability. Genes with fragile (unrobust) transcriptional regulatory program under normal growth condition could be readily reprogrammed to significantly modulate gene expression upon changing conditions. They also have high evolutionary rates of gene expression. We further showed that the fragile transcriptional regulatory program is a major source of expression variability.</p> <p>Conclusion</p> <p>We showed that activity-redundant TFs guarantee the robustness of transcriptional regulatory programs, and the fragility of transcriptional regulatory program plays a major role in gene expression variability. These findings reveal the mechanisms underlying robust transcription and expression variability.</p

Insights into distinct regulatory modes of nucleosome positioning

<p>Abstract</p> <p>Background</p> <p>The nucleosome is the fundamental unit of eukaryotic genomes. Experimental evidence suggests that the genomic DNA sequence and a variety of protein factors contribute to nucleosome positioning <it>in vivo</it>. However, how nucleosome positioning is determined locally is still largely unknown.</p> <p>Results</p> <p>We found that transcription factor binding sites (TFBSs) with particular nucleosomal contexts show a preference to reside on specific chromosomes. We identified four typical gene classes associated with distinct regulatory modes of nucleosome positioning, and further showed that they are distinguished by transcriptional regulation patterns. The first mode involves the cooperativity between chromatin remodeling and stable transcription factor (TF)-DNA binding that is linked to high intrinsic DNA binding affinities, evicting nucleosomes from favorable DNA sequences. The second is the DNA-encoded low nucleosome occupancy that is associated with high gene activity. The third is through chromatin remodeling and histone acetylation, sliding nucleosomes along DNA. This mode is linked to more cryptic sites for TF binding. The last consists of the nucleosome-enriched organization driven by other factors that overrides nucleosome sequence preferences. In addition, we showed that high polymerase II (Pol II) occupancy is associated with high nucleosome occupancy around the transcription start site (TSS).</p> <p>Conclusions</p> <p>We identified four different regulatory modes of nucleosome positioning and gave insights into mechanisms that specify promoter nucleosome location. We suggest two distinct modes of recruitment of Pol II, which are selectively employed by different genes.</p

Behavior of CFRP Plate in Simulated ICCP System of Concrete Structures

An innovative effort was made to utilize carbon fiber reinforced polymer (CFRP) plate as an anode in impressed current cathodic protection (ICCP) of reinforced concrete structure. The feasibility was explored by bonding CFRP strips to concrete and then applying protection current through CFRP strips to steel rebar in concrete. Service life and performance of CFRP plate were investigated in simulated ICCP systems with various configurations. Steel potential results confirmed that the steel rebar in concrete maintained at a satisfactory level with the applied protection current. It is shown that CFRP strips can be successfully used in various solutions as an anode material

Two distinct modes of nucleosome modulation associated with different degrees of dependence of nucleosome positioning on the underlying DNA sequence

<p>Abstract</p> <p>Background</p> <p>The nucleosome is the fundamental unit of eukaryotic genomes. Its positioning plays a central role in diverse cellular processes that rely on access to genomic DNA. Experimental evidence suggests that the genomic DNA sequence is one important determinant of nucleosome positioning. Yet it is less clear whether the role of the underlying DNA sequence in nucleosome positioning varies across different promoters. Whether different determinants of nucleosome positioning have characteristic influences on nucleosome modulation also remains to be elucidated.</p> <p>Results</p> <p>We identified two typical promoter classes in yeast associated with high or low dependence of nucleosome positioning on the underlying DNA sequence, respectively. Importantly, the two classes have low or high intrinsic sequence preferences for nucleosomes, respectively. The two classes are further distinguished by multiple promoter features, including nucleosome occupancy, nucleosome fuzziness, H2A.Z occupancy, changes in nucleosome positions before and after transcriptional perturbation, and gene activity. Both classes have significantly high turnover rates of histone H3, but employ distinct modes of nucleosome modulation: The first class is characterized by hyperacetylation, whereas the second class is highly regulated by ATP-dependent chromatin remodelling.</p> <p>Conclusion</p> <p>Our results, coupled with the known features of nucleosome modulation, suggest that the two distinct modes of nucleosome modulation selectively employed by different genes are linked with the intrinsic sequence preferences for nucleosomes. The difference in modes of nucleosome modulation can account for the difference in the contribution of DNA sequence to nucleosome positioning between both promoter classes.</p

Genome-wide analysis of interactions between ATP-dependent chromatin remodeling and histone modifications

<p>Abstract</p> <p>Background</p> <p>ATP-dependent chromatin remodeling and the covalent modification of histones play central roles in determining chromatin structure and function. Although several specific interactions between these two activities have been elaborated, the global landscape remains to be elucidated.</p> <p>Results</p> <p>In this paper, we have developed a computational method to generate the first genome-wide landscape of interactions between ATP-dependent chromatin remodeling and the covalent modification of histones in <it>Saccharomyces cerevisiae</it>. Our method succeeds in identifying known interactions and uncovers many previously unknown interactions between these two activities. Analysis of the genome-wide picture revealed that transcription-related modifications tend to interact with more chromatin remodelers. Our results also demonstrate that most chromatin remodeling-modification interactions act via interactions of remodelers with both histone-modifying enzymes and histone residues. We also found that the co-occurrence of both modification and remodeling has significantly different influences on multiple gene features (e.g. nucleosome occupancy) compared with the presence of either one.</p> <p>Conclusion</p> <p>We gave the first genome-wide picture of ATP-dependent chromatin remodeling-histone modification interactions. We also revealed how these two activities work together to regulate chromatin structure and function. Our results suggest that distinct strategies for regulating chromatin activity are selectively employed by genes with different properties.</p

Genome-wide analysis of the effect of histone modifications on the coexpression of neighboring genes in Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Neighboring gene pairs in the genome of <it>Saccharomyces cerevisiae </it>have a tendency to be expressed at the same time. The distribution of histone modifications along chromatin fibers is suggested to be an important mechanism responsible for such coexpression. However, the extent of the contribution of histone modifications to the coexpression of neighboring genes is unclear.</p> <p>Results</p> <p>We investigated the similarity of histone modification between neighboring genes using autocorrelation analysis and composite profiles. Our analysis showed that neighboring genes had similar levels or changes of histone modifications, especially those transcribed in the same direction. The similarities, however, were restricted to 1 or 2 neighboring genes. Moreover, the expression of a gene was significantly correlated with histone modification of its neighboring gene(s), but this was limited to only 1 or 2 neighbors. Using a hidden Markov model (HMM), we found more than 2000 chromatin domains with similar acetylation changes as the cultures changed and a considerable number of these domains covered 2-4 genes. Gene pairs within domains exhibited a higher level of coexpression than random pairs and shared similar functions.</p> <p>Conclusions</p> <p>The results of this study suggest that similar histone modifications occur within only a small local chromatin region in yeast. The modifications generally have an effect on coexpression with only 1 or 2 neighboring genes. Some blocking mechanism(s) might strictly restrain the distribution of histone modifications in yeast.</p

Gobi agriculture: an innovative farming system that increases energy and water use efficiencies. A review

International audienceAbstractIn populated regions/countries with fast economic development, such as Africa, China, and India, arable land is rapidly shrinking due to urban construction and other industrial uses for the land. This creates unprecedented challenges to produce enough food to satisfy the increased food demands. Can the millions of desert-like, non-arable hectares be developed for food production? Can the abundantly available solar energy be used for crop production in controlled environments, such as solar-based greenhouses? Here, we review an innovative cultivation system, namely “Gobi agriculture.” We find that the innovative Gobi agriculture system has six unique characteristics: (i) it uses desert-like land resources with solar energy as the only energy source to produce fresh fruit and vegetables year-round, unlike conventional greenhouse production where the energy need is satisfied via burning fossil fuels or electrical consumption; (ii) clusters of individual cultivation units are made using locally available materials such as clay soil for the north walls of the facilities; (iii) land productivity (fresh produce per unit land per year) is 10–27 times higher and crop water use efficiency 20–35 times greater than traditional open-field, irrigated cultivation systems; (iv) crop nutrients are provided mainly via locally-made organic substrates, which reduce synthetic inorganic fertilizer use in crop production; (v) products have a lower environmental footprint than open-field cultivation due to solar energy as the only energy source and high crop yields per unit of input; and (vi) it creates rural employment, which improves the stability of rural communities. While this system has been described as a “Gobi-land miracle” for socioeconomic development, many challenges need to be addressed, such as water constraints, product safety, and ecological implications. We suggest that relevant policies are developed to ensure that the system boosts food production and enhances rural socioeconomics while protecting the fragile ecological environment

Ag-Mg antisite defect induced high thermoelectric performance of α-MgAgSb

Engineering atomic-scale native point defects has become an attractive strategy to improve the performance of thermoelectric materials. Here, we theoretically predict that Ag-Mg antisite defects as shallow acceptors can be more stable than other intrinsic defects under Mg-poor-Ag/Sb-rich conditions. Under more Mg-rich conditions, Ag vacancy dominates the intrinsic defects. The p-type conduction behavior of experimentally synthesized ¿-MgAgSb mainly comes from Ag vacancies and Ag antisites (Ag on Mg sites), which act as shallow acceptors. Ag-Mg antisite defects significantly increase the thermoelectric performance of ¿-MgAgSb by increasing the number of band valleys near the Fermi level. For Li-doped ¿-MgAgSb, under more Mg-rich conditions, Li will substitute on Ag sites rather than on Mg sites and may achieve high thermoelectric performance. A secondary valence band is revealed in ¿-MgAgSb with 14 conducting carrier pockets

Viral infection of an estuarine Synechococcus influences its co-occurring heterotrophic bacterial community in the culture

Viruses are infectious and abundant in the marine environment. Viral lysis of host cells releases organic matter and nutrients that affect the surrounding microbial community. Synechococcus are important primary producers in the ocean and they are subject to frequent viral infection. In the laboratory, Synechococcus cultures are often associated with bacteria and such a co-existence relationship appears to be important to the growth and stability of Synechococcus. However, we know little about how viral lysis of Synechococcus affects the co-existing bacteria in the culture. This study investigated the influence of viral infection of Synechococcus on co-occurring bacterial community in the culture. We analyzed the community composition, diversity, predicted functions of the bacterial community, and its correlations with fluorescent dissolved organic matter (FDOM) components and nutrients after introducing a cyanophage to the Synechococcus culture. Cyanophage infection altered the bacterial community structure and increased the bacterial diversity and richness. Increased bacterial groups such as Bacteroidetes and Alphaproteobacteria and decreased bacterial groups such as Gammaproteobacteria were observed. Moreover, cyanophage infection reduced bacterial interactions but enhanced correlations between the dominant bacterial taxa and nutrients. Unique FDOM components were observed in the cyanophage-added culture. Fluorescence intensities of FDOM components varied across the cyanophage-infection process. Decreased nitrate and increased ammonium and phosphate in the cyanophage-added culture coupled with the viral progeny production and increased substance transport and metabolism potentials of the bacterial community. Furthermore, increased potentials in methane metabolism and aromatic compound degradation of the bacterial community were observed in the cyanophage-added culture, suggesting that cyanophage infections contribute to the production of methane-related compounds and refractory organic matter in a microcosm like environment. This study has the potential to deepen our understanding of the impact of viral lysis of cyanobacteria on microbial community in the surrounding water