SUMMARYINO80 is a conserved chromatin-remodeling factor in eukaryotes. While a previous study reported that the Arabidopsis thaliana INO80 (AtINO80) is required for somatic homologous recombination (HR), the role of AtINO80 in plant growth and development remains obscure. Here, we identified and characterized two independent atino80 mutant alleles, atino80-5 and atino80-6, which display similar and pleiotropic phenotypes, including smaller plant and organ size, and late flowering. Under standard growth conditions, atino80-5 showed decreased HR; however, after genotoxic treatment, HR in the mutant increased, accompanied by more DNA double-strand breaks and stronger cellular responses. Transcription analysis showed that many developmental and environmental responsive genes are overrepresented in the perturbed genes in atino80-5. These genes significantly overlapped with the category of H2A.Z body-enriched genes. AtINO80 also interacts with H2A.Z, and facilitates the enrichment of H2A.Z at the ends of the key flowering repressor genes FLC and MAF4/5. Our characterization of the atino80-5 and atino80-6 mutants confirms and extends the previous AtINO80 study, and provides perspectives for linking studies of epigenetic mechanisms involved in plant chromatin stability with plant response to developmental and environmental cues.

NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) defines an evolutionarily conserved family of histone chaperones and loss of function of the NAP1 family genes () and causes abnormal root hair formation. Yet, the underlying molecular mechanisms remain unclear. Here, we show that NRP1 interacts with the transcription factor WEREWOLF (WER) in vitro and in vivo and enriches at the () promoter in a WER-dependent manner. Crystallographic analysis indicates that NRP1 forms a dimer via its N-terminal α-helix. Mutants of NRP1 that either disrupt the α-helix dimerization or remove the C-terminal acidic tail, impair its binding to histones and WER and concomitantly lead to failure to activate transcription and to rescue the mutant phenotype. Our results further demonstrate that WER-dependent enrichment of NRP1 at the promoter is involved in local histone eviction and nucleosome loss in vivo. Biochemical competition assays imply that the association between NRP1 and histones may counteract the inhibitory effect of histones on the WER-DNA interaction. Collectively, our study provides important insight into the molecular mechanisms by which histone chaperones are recruited to target chromatin via interaction with a gene-specific transcription factor to moderate chromatin structure for proper root hair development.

FGF-10 can prevent or reduce lung specific inflammation due to traumatic or infectious lung injury. However, the exact mechanisms are poorly characterized. Additionally, the effect of FGF-10 on lung-resident mesenchymal stem cells (LR-MSCs) has not been studied. To better characterize the effect of FGF-10 on LR-MSCs, FGF-10 was intratracheally delivered into the lungs of rats. Three days after instillation, bronchoalveolar lavage was performed and plastic-adherent cells were cultured, characterized and then delivered therapeutically to rats after LPS intratracheal instillation. Immunophenotyping analysis of FGF-10 mobilized and cultured cells revealed expression of the MSC markers CD29, CD73, CD90, and CD105, and the absence of the hematopoietic lineage markers CD34 and CD45. Multipotency of these cells was demonstrated by their capacity to differentiate into osteocytes, adipocytes, and chondrocytes. Delivery of LR-MSCs into the lungs after LPS injury reduced the inflammatory response as evidenced by decreased wet-to-dry ratio, reduced neutrophil and leukocyte recruitment and decreased inflammatory cytokines compared to control rats. Lastly, direct delivery of FGF-10 in the lungs of rats led to an increase of LR-MSCs in the treated lungs, suggesting that the protective effect of FGF-10 might be mediated, in part, by the mobilization of LR-MSCs in lungs.

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African swine fever virus (ASFV) can cause highly lethal disease in pigs and is becoming a global threat. ASFV DNA Polymerase X (AsfvPolX) is the most distinctive DNA polymerase identified to date; it lacks two DNA-binding domains (the thumb domain and 8-KD domain) conserved in the homologous proteins. AsfvPolX catalyzes the gap-filling reaction during the DNA repair process of the ASFV virus genome; it is highly error prone and plays an important role during the strategic mutagenesis of the viral genome. The structural basis underlying the natural substrate binding and the most frequent dG:dGTP misincorporation of AsfvPolX remain poorly understood. Here, we report eight AsfvPolX complex structures; our structures demonstrate that AsfvPolX has one unique 5′-phosphate (5′-P) binding pocket, which can favor the productive catalytic complex assembly and enhance the dGTP misincorporation efficiency. In combination with mutagenesis and in vitro catalytic assays, our study also reveals the functional roles of the platform His115-Arg127 and the hydrophobic residues Val120 and Leu123 in dG:dGTP misincorporation and can provide information for rational drug design to help combat ASFV in the future.

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Claudin-3, -4 and -18 released into the alveolar compartment is highly associated with barrier function loss caused by alveolar epithelial injury.

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