Epigenetic inheritance of DNA methylation in mammals requires a multifunctional protein UHRF1, which is believed to recruit DNMT1 to DNA replication forks through a unique hemi-methylated CpG-binding activity. Here we demonstrate that the UHRF1 mutants deficient in binding either hemi-methylated CpG or H3K9me2/3, but not both, are able to associate with pericentric heterochromatin, recruit Dnmt1 and partially rescue DNA methylation defects in mouse Uhrf1 null ES cells. Furthermore, we present evidence that the flip out of the methylated cytosine induced by UHRF1 binding is unlikely essential for subsequent DNA methylation by DNMT1. Together, our study demonstrates that UHRF1 can target DNMT1 for DNA maintenance methylation through binding either H3K9me2/3 or hemi-methylated CpG, and that the presence of both binding activities ensures high fidelity DNA maintenance methylation. In addition, our study indicates that UHRF1 mediates cross-talk between H3K9 methylation and DNA methylation at the level of DNA methylation maintenance.

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Recent studies demonstrate that UHRF1 is required for DNA methylation maintenance by targeting DNMT1 to DNA replication foci, presumably through its unique hemi-methylated DNA-binding activity and interaction with DNMT1. UHRF2, another member of the UHRF family proteins, is highly similar to UHRF1 in both sequence and structure, raising questions about its role in DNA methylation. In this study, we demonstrate that, like UHRF1, UHRF2 also binds preferentially to methylated histone H3 lysine 9 (H3K9) through its conserved tudor domain and hemi-methylated DNA through the SET and Ring associated domain. Like UHRF1, UHRF2 is enriched in pericentric heterochromatin. The heterochromatin localization depends to large extent on its methylated H3K9-binding activity and to less extent on its methylated DNA-binding activity. Coimmunoprecipitation experiments demonstrate that both UHRF1 and UHRF2 interact with DNMT1, DNMT3a, DNMT3b and G9a. Despite all these conserved functions, we find that UHRF2 is not able to rescue the DNA methylation defect in Uhrf1 null mouse embryonic stem cells. This can be attributed to the inability for UHRF2 to recruit DNMT1 to replication foci during S phase of the cell cycle. Indeed, we find that while UHRF1 interacts with DNMT1 in an S phase-dependent manner in cells, UHRF2 does not. Thus, our study demonstrates that UHRF2 and UHRF1 are not functionally redundant in DNA methylation maintenance and reveals the cell-cycle-dependent interaction between UHRF1 and DNMT1 as a key regulatory mechanism targeting DNMT1 for DNA methylation.

The Changjiang (Yangtze) estuarine and coastal waters are characterized by suspended sediments over a wide range of concentrations from 20 to 2,500 mg l −1 .Suspended sediment plays important roles in the estuarine and coastal system and environment. Previous algorithms for satellite estimates of suspended sediment concentration (SSC) showed a great limitation in that only low to moderate concentrations (up to 50 mg l −1 ) could be reliably estimated. In this study, we developed a semi-empirical radiative transfer (SERT) model with physically based empirical coefficients to estimate SSC from MERIS data over turbid waters with a much wider range of SSC. The model was based on the Kubelka-Munk two-stream approximation of radiative transfer theory and calibrated using datasets from in situ measurements and outdoor controlled tank experiments. The results show that the sensitivity and saturation level of remote-sensing reflectance to SSC are dependent on wavelengths and SSC levels. Therefore, the SERT model, coupled with a multiconditional algorithm scheme adapted to satellite retrieval of wide-range SSC, was proposed. Results suggest that this method is more effective and accurate in the estimation of SSC over turbid waters.

Amplitude changes without latency changes may be due to changes in tube position alone during surgery, but could still reflect a neurophysiologic event; amplitude changes during neuropraxic injury merit additional investigation. Thus, the combined event (concordant amplitude decrease and latency increase) serves as an appropriate adverse EMG event correlating with impending neural injury. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1004-E1008, 2016.