Crosstalk between H2A variant-specific modifications impacts vital cell functions

Selection of C-terminal motifs participated in evolution of distinct histone H2A variants. Hybrid types of variants combining motifs from distinct H2A classes are extremely rare. This suggests that the proximity between the motif cases interferes with their function. We studied this question in flowering plants that evolved sporadically a hybrid H2A variant combining the SQ motif of H2A.X that participates in the DNA damage response with the KSPK motif of H2A.W that stabilizes heterochromatin. Our inventory of PTMs of H2A.W variants showed that in vivo the cell cycle-dependent kinase CDKA phosphorylates the KSPK motif of H2A. W but only in absence of an SQ motif. Phosphomimicry of KSPK prevented DNA damage response by the SQ motif of the hybrid H2A.W/X variant. In a synthetic yeast expressing the hybrid H2A.W/X variant, phosphorylation of KSPK prevented binding of the BRCT-domain protein Mdb1 to phosphorylated SQ and impaired response to DNA damage. Our findings illustrate that PTMs mediate interference between the function of H2A variant specific C-terminal motifs. Such interference could explain the mutual exclusion of motifs that led to evolution of H2A variants.Fil: Schmücker, Anna. Austrian Academy Of Sciences (oaw);Fil: Lei, Bingkun. Austrian Academy Of Sciences (oaw);Fil: Lorkovic, Zdravko J.. Ludwig Maximilians Universitat; AlemaniaFil: Capella, Matias. Ludwig Maximilians Universitat; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Braun, Sigurd. Ludwig Maximilians Universitat; AlemaniaFil: Bourguet, Pierre. Gregor Mendel Institute Of Molecular Plant Biology; Austria. Université Clermont Auvergne; FranciaFil: Mathieu, Olivier. Université Clermont Auvergne; FranciaFil: Mechtler, Karl. Gregor Mendel Institute Of Molecular Plant Biology; AustriaFil: Berger, Frédéric. Gregor Mendel Institute Of Molecular Plant Biology; Austri

A Synthetic Approach to Reconstruct the Evolutionary and Functional Innovations of the Plant Histone Variant H2A.W

Diversification of histone variants is marked by the acquisition of distinct motifs and functional properties through convergent evolution.1–4 H2A variants are distinguished by specific C-terminal motifs and tend to be segregated within defined domains of the genome.5,6 Whether evolution of these motifs pre-dated the evolution of segregation mechanisms or vice versa has remained unclear. A suitable model to address this question is the variant H2A.W, which evolved in plants through acquisition of a KSPK motif7 and is tightly associated with heterochromatin.4 We used fission yeast, where chromatin is naturally devoid of H2A.W, to study the impact of engineered chimeras combining yeast H2A with the KSPK motif. Biochemical assays showed that the KSPK motif conferred nucleosomes with specific properties. Despite uniform incorporation of the engineered H2A chimeras in the yeast genome, the KSPK motif specifically affected heterochromatin composition and function. We conclude that the KSPK motif promotes chromatin properties in yeast that are comparable to the properties and function of H2A.W in plant heterochromatin. We propose that the selection of functional motifs confer histone variants with properties that impact primarily a specific chromatin state. The association between a new histone variant and a preferred chromatin state can thus provide a setting for the evolution of mechanisms that segregate the new variant to this state, thereby enhancing the impact of the selected properties of the variant on genome activity.Fil: Lei, Bingkun. Gregor Mendel Institute; AustriaFil: Capella, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Montgomery, Sean A.. Gregor Mendel Institute; AustriaFil: Borg, Michael. Gregor Mendel Institute; AustriaFil: Osakabe, Akihisa. Gregor Mendel Institute; AustriaFil: Goiser, Malgorzata. Gregor Mendel Institute; AustriaFil: Muhammad, Abubakar. Universitat Technical Zu Munich; AlemaniaFil: Braun, Sigurd. Universitat Technical Zu Munich; AlemaniaFil: Berger, Frédéric. Gregor Mendel Institute; Austri

High accuracy microwave frequency measurement based on single-drive dual-parallel Mach-Zehnder modulator

A novel approach for broadband microwave frequency measurement by employing a single-drive dual-parallel Mach-Zehnder modulator is proposed and experimentally demonstrated. Based on bias manipulations of the modulator, conventional frequency-to-power mapping technique is developed by performing a two-stage frequency measurement cooperating with digital signal processing. In the experiment, 10GHz measurement range is guaranteed and the average uncertainty of estimated microwave frequency is 5.4MHz, which verifies the measurement accuracy is significantly improved by achieving an unprecedented 10−3 relative error. This high accuracy frequency measurement technique is a promising candidate for high-speed electronic warfare and defense applications. A novel approach for broadband microwave frequency measurement by employing a single-drive dual-parallel Mach-Zehnder modulator is proposed and experimentally demonstrated. Based on bias manipulations of the modulator, conventional frequency-to-power mapping technique is developed by performing a two-stage frequency measurement cooperating with digital signal processing. In the experiment, 10GHz measurement range is guaranteed and the average uncertainty of estimated microwave frequency is 5.4MHz, which verifies the measurement accuracy is significantly improved by achieving an unprecedented 10−3 relative error. This high accuracy frequency measurement technique is a promising candidate for high-speed electronic warfare and defense applications

Impact of psychological contract in knowledge sharing: A case study from Industrial Cluster Enterprises

Psychological contract plays a critical role in knowledge sharing. In this paper, we have analyzed the influence of psychological contract and affective commitment to knowledge sharing in China. After using AMOS software for data processing by employing data on the questionnaire, which indicated that there are high consistency and stability and good convergence validity and construction reliability among variables, the multiple Ordinary Least Square(OLS) method was utilized in the study. There are 183 questionnaires were received in the experiment. After analysis, 157 questionnaires were valid for the research; the effective recovery rate was about to 86%. Based on the study, the conclusion could be conducted that the relationship contract and development contract of enterprise technical staff have positive impacts to knowledge sharing, On the contrary, the transaction contract has a negative impact to knowledge sharing

Identification of novel genes involved in DNA damage response by screening a genome-wide <it>Schizosaccharomyces pombe</it> deletion library

<p>Abstract</p> <p>Background</p> <p>DNA damage response (DDR) plays pivotal roles in maintaining genome integrity and stability. An effective DDR requires the involvement of hundreds of genes that compose a complicated network. Because DDR is highly conserved in evolution, studies in lower eukaryotes can provide valuable information to elucidate the mechanism in higher organisms. Fission yeast (<it>Schizosaccharomyces pombe</it>) has emerged as an excellent model for DDR research in recent years. To identify novel genes involved in DDR, we screened a genome-wide <it>S</it>. <it>pombe</it> haploid deletion library against six different DNA damage reagents. The library covered 90.5% of the nonessential genes of <it>S. pombe</it>.</p> <p>Results</p> <p>We have identified 52 genes that were actively involved in DDR. Among the 52 genes, 20 genes were linked to DDR for the first time. Flow cytometry analysis of the repair defective mutants revealed that most of them exhibited a defect in cell cycle progression, and some caused genome instability. Microarray analysis and genetic complementation assays were carried out to characterize 6 of the novel DDR genes in more detail. Data suggested that <it>SPBC2A9.02</it> and <it>SPAC27D7.08c</it> were required for efficient DNA replication initiation because they interacted genetically with DNA replication initiation proteins Abp1 and Abp2. In addition, deletion of <it>sgf73</it>⁺, <it>meu29</it>⁺, <it>sec65</it>⁺ or <it>pab1</it>⁺ caused improper cytokinesis and DNA re-replication, which contributed to the diploidization in the mutants.</p> <p>Conclusions</p> <p>A genome-wide screen of genes involved in DDR emphasized the key role of cell cycle control in the DDR network. Characterization of novel genes identified in the screen helps to elucidate the mechanism of the DDR network and provides valuable clues for understanding genome stability in higher eukaryotes.</p

Crosstalk between H2A variant-specific modifications impacts vital cell functions

International audienceSelection of C-terminal motifs participated in evolution of distinct histone H2A variants. Hybrid types of variants combining motifs from distinct H2A classes are extremely rare. This suggests that the proximity between the motif cases interferes with their function. We studied this question in flowering plants that evolved sporadically a hybrid H2A variant combining the SQ motif of H2A.X that participates in the DNA damage response with the KSPK motif of H2A.W that stabilizes heterochromatin. Our inventory of PTMs of H2A.W variants showed that in vivo the cell cycle-dependent kinase CDKA phosphorylates the KSPK motif of H2A.W but only in absence of an SQ motif. Phosphomimicry of KSPK prevented DNA damage response by the SQ motif of the hybrid H2A.W/X variant. In a synthetic yeast expressing the hybrid H2A.W/X variant, phosphorylation of KSPK prevented binding of the BRCT-domain protein Mdb1 to phosphorylated SQ and impaired response to DNA damage. Our findings illustrate that PTMs mediate interference between the function of H2A variant specific C-terminal motifs. Such interference could explain the mutual exclusion of motifs that led to evolution of H2A variants

Enhanced strength and ductility of metal composites with intragranularly dispersed reinforcements by additive manufacturing

10.1080/21663831.2022.2153630Materials Research Letters115360-36

Moisture-tailored 2D Dion–Jacobson perovskites for reconfigurable optoelectronics

Humidity- and moisture-induced degradation has been a longstanding problem in perovskite materials, affecting their long-term stability during applications. Counterintuitively, the moisture is leveraged to tailor the reversible hydrochromic behaviors of a new series of 2D Dion-Jacobson (DJ) perovskites for reconfigurable optoelectronics. In particular, the hydrogen bonds between organic cations and water molecules can be dynamically modulated via moisture removal/exposure. Remarkably, such modulation confines the movement of the organic cations close to the original position, preventing their escape from crystal lattices. Furthermore, this mechanism is elucidated by theoretical analysis using first-principles calculations and confirmed with the experimental characterizations. The reversible fluorescent transition 2D DJ perovskites show excellent cyclical properties, presenting untapped opportunities for reconfigurable optoelectronic applications. As a proof-of-concept demonstration, an anti-counterfeiting display is shown based on patterned reversible 2D DJ perovskites. The results represent a new avenue of reconfigurable optoelectronic application with 2D DJ perovskites for humidity detection, anti-counterfeiting, sensing, and other emerging photoelectric intelligent technologies.Nanyang Technological UniversityThis work was supported by the National Natural Science Foundation of China (Grant Nos. 52172162, 52072349 and 11704139). Z.D. acknowledges support from the Fundamental Research Funds for the Central Universities, China University of Geosciences (Wuhan) (No.162301202610), the Natural Science Foundation of Guangdong Province(2022A1515012145), and Shenzhen Science and Technology Program(JCYJ20220530162403007). G.L. acknowledges support from the Natural Science Foundation of Zhejiang Province (LR22E020004). Y.X. acknowledges support from the Natual Science Foundation of Hubei Province(No. 2021CFB574). G.H. acknowledges the support of start-up grant from Nanyang Technological University

CircNUP54 promotes hepatocellular carcinoma progression via facilitating HuR cytoplasmic export and stabilizing BIRC3 mRNA

Abstract Circular RNAs (circRNAs) have been implicated in tumorigenesis and progression of various cancers. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) have not been fully elucidated. Herein, a new oncogenic circRNA, hsa_circ_0070039 (circNUP54), was identified to be significantly upregulated in HCC through circRNA sequencing. As verified in 68 HCC samples, circNUP54 overexpression was correlated with aggressive cancerous behaviors and poor outcomes. Moreover, the function experiments showed that knockdown of circNUP54 inhibited the malignant progression of HCC in vitro and in vivo, whereas overexpression of circNUP54 had the opposite role. Mechanistic investigations carried out by RNA pull-down, RNA immunoprecipitation, and immunofluorescence revealed that circNUP54 interacted with the RNA-binding protein Hu-antigen R (HuR) and promoted its cytoplasmic export. The cytoplasmic accumulation of HuR stabilized the downstream BIRC3 mRNA through its binding to the 3′ UTR region. Consequently, the encoded protein of BIRC3, cellular inhibitor of apoptosis 2 (cIAP2), proceeded to activate the NF-κB signal pathway and ultimately contributed to HCC progression. In addition, depletion of BIRC3 rescued the pro-tumorigenic effect of circNUP54 on HCC cells. Overall, this study demonstrated that circNUP54 facilitates HCC progression via regulating the HuR/BIRC3/NF-κB axis, which may serve as a promising therapeutic target for HCC treatment