Management of security activities at innovative-active enterprises

The article identifies the fundamental problems of innovation as a factor in strengthening the economic security of an enterprise in the context of globalization and integration of the world’s economic space. The factors that have a direct impact on innovation activity both in the country and in the world have been investigated. Clustering of individual countries was carried out and Ukraine’s place among them was determined according to the Global Innovation Index. Using the software packages MS Excel and CurveExpert 5.0, a study of the index of innovative efficiency in Ukraine was carried out; dynamics of financing innovative activities in Ukraine, as well as the impact of the level of capital investment on the volume of financing innovative activities. It is proposed to assess the level of economic security of an enterprise based on indicators of its innovative development. The features of interpreting the concept of “innovative activity of enterprises” have been investigated. The sequence and interconnection of such categories as innovative potential, innovative activity, and innovative activity are analyzed. The structure of the process of innovation activity has been investigated. The rhombus of innovative activity is analyzed, which is formed from the following elements: receptivity to new things – provision of resources – communication and organization of the innovation process – a measure of competence. In the study of the specifics of the management of innovative-active enterprises, the analysis of the features and comparison of the differences between innovation activity and other types of economic activity was carried out. The structure of the process of managing innovatively active enterprises has been developed, taking into account aspects of the safety of activities. The prospect of further research identified a thorough analysis of the features of the management process of innovatively active enterprises, considering the impact of global risks and threats. The principal purpose of the article is to study the essence and main characteristics of innovatively active enterprises in the study's context of the security aspect

Cooperation between the INO80 Complex and Histone Chaperones Determines Adaptation of Stress Gene Transcription in the Yeast Saccharomyces cerevisiae▿ †

In yeast, environmental stresses provoke sudden and dramatic increases in gene expression at stress-inducible loci. Stress gene transcription is accompanied by the transient eviction of histones from the promoter and the transcribed regions of these genes. We found that mutants defective in subunits of the INO80 complex, as well as in several histone chaperone systems, exhibit extended expression windows that can be correlated with a distinct delay in histone redeposition during adaptation. Surprisingly, Ino80 became associated with the ORFs of stress genes in a stress-specific way, suggesting a direct function in the repression during adaptation. This recruitment required elongation by RNA polymerase (Pol) II but none of the histone modifications that are usually associated with active transcription, such as H3 K4/K36 methylation. A mutant lacking the Asf1-associated H3K56 acetyltransferase Rtt109 or Asf1 itself also showed enhanced stress-induced transcript levels. Genetic data, however, suggest that Asf1 and Rtt109 function in parallel with INO80 to restore histone homeostasis, whereas Spt6 seems to have a function that overlaps that of the chromatin remodeler. Thus, chromatin remodeling by INO80 in cooperation with Spt6 determines the shape of the expression profile under acute stress conditions, possibly by an elongation-dependent mechanism

A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis.

Despite their classical role as transcriptional repressors, several histone deacetylases, including the baker's yeast Set3/Hos2 complex (Set3C), facilitate gene expression. In the dimorphic human pathogen Candida albicans, the homologue of the Set3C inhibits the yeast-to-filament transition, but the precise molecular details of this function have remained elusive. Here, we use a combination of ChIP-Seq and RNA-Seq to show that the Set3C acts as a transcriptional co-factor of metabolic and morphogenesis-related genes in C. albicans. Binding of the Set3C correlates with gene expression during fungal morphogenesis; yet, surprisingly, deletion of SET3 leaves the steady-state expression level of most genes unchanged, both during exponential yeast-phase growth and during the yeast-filament transition. Fine temporal resolution of transcription in cells undergoing this transition revealed that the Set3C modulates transient expression changes of key morphogenesis-related genes. These include a transcription factor cluster comprising of NRG1, EFG1, BRG1, and TEC1, which form a regulatory circuit controlling hyphal differentiation. Set3C appears to restrict the factors by modulating their transcription kinetics, and the hyperfilamentous phenotype of SET3-deficient cells can be reverted by mutating the circuit factors. These results indicate that the chromatin status at coding regions represents a dynamic platform influencing transcription kinetics. Moreover, we suggest that transcription at the coding sequence can be transiently decoupled from potentially conflicting promoter information in dynamic environments

The histone chaperone HIR maintains chromatin states to control nitrogen assimilation and fungal virulence

Adaptation to changing environments and immune evasion is pivotal for fitness of pathogens. Yet, the underlying mechanisms remain largely unknown. Adaptation is governed by dynamic transcriptional re-programming, which is tightly connected to chromatin architecture. Here, we report a pivotal role for the HIR histone chaperone complex in modulating virulence of the human fungal pathogen Candida albicans. Genetic ablation of HIR function alters chromatin accessibility linked to aberrant transcriptional responses to protein as nitrogen source. This accelerates metabolic adaptation and increases the release of extracellular proteases, which enables scavenging of alternative nitrogen sources. Furthermore, HIR controls fungal virulence, as HIR1 deletion leads to differential recognition by immune cells and hypervirulence in a mouse model of systemic infection. This work provides mechanistic insights into chromatin-coupled regulatory mechanisms that fine-tune pathogen gene expression and virulence. Furthermore, the data point toward the requirement of refined screening approaches to exploit chromatin modifications as antifungal strategies

A Histone Deacetylase Adjusts Transcription Kinetics at Coding Sequences during <em>Candida albicans</em> Morphogenesis

<div><p>Despite their classical role as transcriptional repressors, several histone deacetylases, including the baker's yeast Set3/Hos2 complex (Set3C), facilitate gene expression. In the dimorphic human pathogen <em>Candida albicans</em>, the homologue of the Set3C inhibits the yeast-to-filament transition, but the precise molecular details of this function have remained elusive. Here, we use a combination of ChIP–Seq and RNA–Seq to show that the Set3C acts as a transcriptional co-factor of metabolic and morphogenesis-related genes in <em>C. albicans</em>. Binding of the Set3C correlates with gene expression during fungal morphogenesis; yet, surprisingly, deletion of <em>SET3</em> leaves the steady-state expression level of most genes unchanged, both during exponential yeast-phase growth and during the yeast-filament transition. Fine temporal resolution of transcription in cells undergoing this transition revealed that the Set3C modulates transient expression changes of key morphogenesis-related genes. These include a transcription factor cluster comprising of <em>NRG1</em>, <em>EFG1</em>, <em>BRG1</em>, and <em>TEC1</em>, which form a regulatory circuit controlling hyphal differentiation. Set3C appears to restrict the factors by modulating their transcription kinetics, and the hyperfilamentous phenotype of <em>SET3</em>-deficient cells can be reverted by mutating the circuit factors. These results indicate that the chromatin status at coding regions represents a dynamic platform influencing transcription kinetics. Moreover, we suggest that transcription at the coding sequence can be transiently decoupled from potentially conflicting promoter information in dynamic environments.</p> </div

The <i>C. albicans</i> Set3C is a coding sequence histone deacetylase.

<p>(A) Architecture of the <i>S. cerevisiae</i> Set3C. The subunits among which physical interaction was confirmed in <i>C. albicans</i> are colored green (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003118#pgen.1003118.s001" target="_blank">Figure S1B</a>). (B) Physical interaction of Set3 and Hos2. Set3-3HA was immunoprecipitated from whole cell extracts and the interaction was probed by immunoblot detection of a Hos2-9myc allele. (C) Read density profiles of one replicate of a Set3-9myc and an untagged control ChIP-Seq experiment. Genes were divided into binding targets (“targets”) and non-targets (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003118#s4" target="_blank">Materials and Methods</a>). Transcription start site (TSS) denotes the start codon and Transcription termination site (TTS) denotes the stop codon. The read density values between the TSS and TTS were calculated to a percentage scale, and 500 bases upstream of the TSS and downstream of the TTS were included. On the bottom panel only genes with a coding region longer than 1 kilobase were included. (D) Definition of CaSet3C refined target gene set. Each dot corresponds to one ORF. Binding targets of RNAPII transcribed genes are defined as having an at least 2-fold enrichment on one axis and an at least 1.5-fold on the other axis (blue box). Target tRNA loci are defined as having an at least 1.5-fold enrichment on both axes. The complete dataset is found in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003118#pgen.1003118.s011" target="_blank">Tables S4</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003118#pgen.1003118.s012" target="_blank">S5</a>. “<i>r</i>” denotes a Pearson's correlation coefficient. (E) The Set3C functions as histone deacetylase <i>in vivo</i>. Top panel: validation of Set3 and Hos2 binding using the indicated probes around the <i>PFK1</i> and <i>tR(CCG)1</i> loci by qPCR. Values are normalized to a fragment of the <i>ADE2</i> locus. Bottom panel: ChIP experiments were performed with antibodies against acetylated histone H4 and the C-terminus of histone H3. The qPCR values at the probe positions were normalized to a fragment of the telomere of Chromosome 7. The ratio of the signal of the acetylated H4 ChIP and H3 ChIP is shown on the y-axis. Data are shown as mean+SD of three independent experiments. Statistical significance was determined by two-tailed t-test relative to the control values. *P<0.05, **P<0.01, ***P<0.001.</p

The Set3C decorates highly transcribed genes.

<p>(A) Correlation of Set binding and RNA expression for the target gene set (defined on <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003118#pgen-1003118-g001" target="_blank">Figure 1D</a>). Each dot corresponds to one gene. The distribution of expression values of the genes belonging to each functional category is shown on the right panel. “<i>r</i>” denotes a Pearson's correlation coefficient. TF stands for the transcription factor cluster (see text). Statistical significance was determined by the Mann-Whitney U-test relative to the “all genes” set. *P<0.05, **P<0.01, ***P<0.001, ns: not significant. (B) Transcript profile of <i>set3</i>Δ/Δ cells by RNA-Seq. The fold change in RNA expression between <i>set3</i>Δ/Δ and wild type cells at each gene is plotted against the expression level of the gene in wild type cells. The direct binding targets and their functional groups are highlighted. The distribution of fold changes of the genes belonging to each functional category is shown on the right panel. Statistical significance was determined by the Mann-Whitney U-test relative to the “all genes” set. *P<0.05, **P<0.01, ***P<0.001, ns: not significant.</p

Yeast protein phosphatase 2A-Cdc55 regulates the transcriptional response to hyperosmolarity stress by regulating Msn2 and Msn4 chromatin recruitment.

We have identified Cdc55, a regulatory B subunit of protein phosphatase 2A (PP2A), as an essential activating factor for stress gene transcription in Saccharomyces cerevisiae. The presence of PP2A-Cdc55 is required for full activation of the environmental stress response mediated by the transcription factors Msn2 and Msn4. We show that PP2A-Cdc55 contributes to sustained nuclear accumulation of Msn2 and Msn4 during hyperosmolarity stress. PP2A-Cdc55 also enhances Msn2-dependent transactivation, required for extended chromatin recruitment of the transcription factor. We analyzed a possible direct regulatory role for PP2A-Cdc55 on the phosphorylation status of Msn2. Detailed mass spectrometric and genetic analysis of Msn2 showed that stress exposure causes immediate transient dephosphorylation of Msn2 which is not dependent on PP2A-Cdc55 activity. Furthermore, the Hog1 mitogen-activated protein kinase pathway activity is not influenced by PP2A-Cdc55. We therefore propose that the PP2A-Cdc55 phosphatase is not involved in cytosolic stress signal perception but is involved in a specific intranuclear mechanism to regulate Msn2 and Msn4 nuclear accumulation and chromatin association under stress conditions.status: publishe

Set3C recruitment predicts induction and depletion predicts repression.

<p>(A) Microscopic images of cells undergoing yeast-to-hypha differentiation. The cells at each time point do not correspond to the cells at the other time points. Scale bar corresponds to 5 µm. (B) Transcript landscape of hyphal cells 30 minutes after induction. The fold change in RNA expression between hyphal and yeast cultures at each gene is plotted against the expression level of the gene in wild type yeast cells measured by RNA-Seq. Each dot represents one gene. Set3C binding targets were defined by Set3C ChIP-Seq experiments (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003118#s4" target="_blank">Materials and Methods</a>). The Set3C target genes are divided into yeast-specific, hypha-specific and constitutively bound subgroups. The distribution of RNA fold changes of the genes belonging to each category is shown on the right panel. Statistical significance was determined by the Mann-Whitney U-test relative to the “all targets” set. *P<0.05, **P<0.01, ***P<0.001, ns: not significant. (C) Correlation of RNA fold change and differential ChIP enrichment signals. Each dot corresponds to one gene, and only the genes defined as Set3C binding targets in at least one phase are shown. “<i>r</i>” denotes a Pearson's correlation coefficient. (D) qPCR verification of the correlation on (C). Histone H4 has two loci in <i>C. albicans</i> (<i>HHF1</i> and <i>HHF22</i>), and the primers used in the qPCR bind alleles of both. Data are shown as mean+SD of three independent experiments. Statistical significance was determined by two-tailed t-test. *P<0.05, **P<0.01, ***P<0.001. (E) Comparison of the gene induction profiles of wild type and <i>set3</i>Δ/Δ cells undergoing hyphal differentiation. Fold change between the hyphal and yeast phases for the two genotypes are plotted on the two axes. Each dot corresponds to one gene. The categories of Set3C binding targets are defined as on (B). “<i>r</i>” denotes a Pearson's correlation coefficient, and “m” denotes the slope of the linear regression.</p