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In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation. [ABSTRACT FROM AUTHOR]

Abstract  The thermal unfolding of Urinary Trypsin Inhibitor (UTI) was studied by several methods: Circular Dichroism (CD), Fluorescence and UV–Vis spectra. Thermal melting of UTI, dissolved in the neutral and basic buffers, was proved to be irreversible and two domains of UTI unfolded simultaneously, but the melting was reversible and the intermediate was observed when pH is lower than 4.2. The result suggested that heat and changes in pH, which had a more important impact on the stabilization of the domain I and the interaction between two domains, might cause different unfolding transitions. A reasonable explanation was deduced for the mechanism of reversible and irreversible thermal unfolding based on the effect of pH on the protein structure, the analysis of thermal transitions and the result of Electron Microscopy: In neutral and basic buffers, the Reactive Central Loop (RCL) in domain II can interact with or insert into the partial expanding domain I and UTI become self-polymerization, however, no aggregation can be observed in acid buffer since low pH and heat destabilized the structure of the domain I and the native conformation can restructure. The interaction between the special structural element RCL and domain I play an important role in the formation of polymer which was different from other two reasons given by other authors—the cleavage of disulfide and the formation of irregular polymer mainly based on hydrophobic interaction. [ABSTRACT FROM AUTHOR]

The article presents the substrate deformation regulates domains rearranged methyltransferase 2 (DRM2)-mediated DNA methylation in plants. Topics include the DNA methylation is a major epigenetic mechanism critical for gene expression and genome stability, the structure-function characterization of DRM2-mediated methylation, and the arginine finger from the catalytic loop intercalates into the nontarget strand of DNA through the minor groove.

IFN-&agr; is a widely used treatment for hepatitis B virus (HBV) infection, and IFN resistance caused by viral and/or host factors is currently a challenging clinical problem. A better understanding of the molecular mechanisms underlying IFN immunotherapy in the treatment of viral infection would be very beneficial clinically and is of immense clinical importance. Calreticulin (CRT) is an endoplasmic reticulum luminal calcium-binding chaperone that is involved in the regulation of calcium homoeostasis, the folding of newly synthesized proteins, and many other cellular functions. However, little is known about the role of CRT in HBV infection. In this study, we observed high levels of CRT expression in the sera and PBMCs of patients with HBV relative to those of healthy individuals. HBV upregulated the expression of CRT at the transcriptional level. Further investigation showed that HBV-induced CRT enhanced HBV replication by antagonizing the IFN pathway. CRT suppressed the production of endogenous IFN-&agr; by reducing the nuclear translocation of IFN regulatory factor-7 but not IFN regulatory factor-3. Furthermore, CRT also suppressed the antiviral activity of IFN-&agr; by inhibiting the phosphorylation of STAT1 and decreasing the expression of two IFN-&agr; downstream effectors, protein kinase R and 2',5'-oligoadenylate synthetase. Our results offer new insights into the pathogenesis of HBV infection and may provide potential targets for anti-HBV therapy. [ABSTRACT FROM AUTHOR]