Anterior gradient 2 (AGR2) is a protein disulfide isomerase that is important for protein processing in the endoplasmic reticulum and is essential for mucin production in the digestive and respiratory tracts. Bi-allelic AGR2 variants were recently found to cause recurrent respiratory infections and failure to thrive with or without diarrhea (RIFTD; MIM # 620233), although the mechanisms behind this condition remain unclear. To date, at least 15 patients with homozygous AGR2 variants have been reported.
View Article and Find Full Text PDFActa Crystallogr B Struct Sci Cryst Eng Mater
December 2024
The odd hydration number has so far been missing in the water-rich magnesium chloride hydrate series (MgCl·nHO). In this study, magnesium chloride heptahydrate, MgCl·7HO (or MgCl·7DO), which forms at high pressures above 2 GPa and high temperatures above 300 K, has been identified. Its structure has been determined by a combination of in-situ single-crystal X-ray diffraction at 2.
View Article and Find Full Text PDFHydrogen bond symmetrisation is the phenomenon where a hydrogen atom is located at the centre of a hydrogen bond. Theoretical studies predict that hydrogen bonds in ice VII eventually undergo symmetrisation upon increasing pressure, involving nuclear quantum effect with significant isotope effect and drastic changes in the elastic properties through several intermediate states with varying hydrogen distribution. Despite numerous experimental studies conducted, the location of hydrogen and hence the transition pressures reported up to date remain inconsistent.
View Article and Find Full Text PDFIce IV is a metastable high-pressure phase of ice in which the water molecules exhibit orientational disorder. Although orientational ordering is commonly observed for other ice phases, it has not been reported for ice IV. We conducted powder neutron diffraction experiments for DCl-doped DO ice IV to investigate its hydrogen ordering.
View Article and Find Full Text PDFUnintegrated retroviral DNA is transcriptionally silenced by host chromatin silencing factors. Here, we used the proteomics of isolated chromatin segments method to reveal viral and host factors associated with unintegrated HIV-1DNA involved in its silencing. By gene silencing using siRNAs, 46 factors were identified as potential repressors of unintegrated HIV-1DNA.
View Article and Find Full Text PDFNuclear localization signal (NLS) of HIV-1 integrase (IN) is implicated in nuclear import of HIV-1 preintegration complex (PIC). Here, we established a multiclass drug-resistant HIV-1 variant (HIV) by consecutively exposing an HIV-1 variant to various antiretroviral agents including IN strand transfer inhibitors (INSTIs). HIV was extremely susceptible to a previously reported HIV-1 protease inhibitor, GRL-142, with IC of 130 femtomolar.
View Article and Find Full Text PDFReplication of genetic material involves the creation of characteristic termini. Determining these termini is important to refine our understanding of the mechanisms involved in maintaining the genomes of cellular organisms and viruses. Here we describe a computational approach combining direct and indirect readouts to detect termini from next-generation short-read sequencing.
View Article and Find Full Text PDFNot only does Marseillevirus bear the name of the city where it was identified, it also encompasses its values and what makes Marseille a wonderful city. Marseillevirus is unique and intriguing. As such, Bryson et al.
View Article and Find Full Text PDFIce polymorphs show extraordinary structural diversity depending on pressure and temperature. The behavior of hydrogen-bond disorder not only is a key ingredient for their structural diversity but also controls their physical properties. However, it has been a challenge to determine the details of the disordered structure in ice polymorphs under pressure, because of the limited observable reciprocal space and inaccuracies related to high-pressure techniques.
View Article and Find Full Text PDFHigh-pressure X-ray and neutron diffraction analyses of an ambient-pressure phase (AP) and two high-pressure phases (HP1 and HP2) of ammonia borane (i.e., NHBH and NDBD) were conducted to investigate the relationship between their crystal structures and dihydrogen bonds.
View Article and Find Full Text PDFThe structure refinement of black phosphorus was performed at pressures of up to 3.2 GPa at room temperature by powder neutron diffraction techniques. The bond lengths and bond angles between the phosphorus atoms at pressures were precisely determined and confirmed to be consistent with those of the previous single crystal x-ray analysis [A.
View Article and Find Full Text PDFAbove 2 GPa the phase diagram of water simplifies considerably and exhibits only two solid phases up to 60 GPa, ice VII and ice VIII. The two phases are related to each other by hydrogen ordering, with the oxygen sublattice being essentially the same. Here we present neutron diffraction data to 15 GPa which reveal that the rate of hydrogen ordering at the ice VII-VIII transition decreases strongly with pressure to reach timescales of minutes at 10 GPa.
View Article and Find Full Text PDFThe aim of the present study was to understand the biology of unintegrated HIV-1 DNA and reveal the mechanisms involved in its transcriptional silencing. We found that histones are loaded on HIV-1 DNA after its nuclear import and before its integration in the host genome. Nucleosome positioning analysis along the unintegrated and integrated viral genomes revealed major differences in nucleosome density and position.
View Article and Find Full Text PDFWater freezes below 0 °C at ambient pressure ordinarily to ice I, with hexagonal stacking sequence. Under certain conditions, ice with a cubic stacking sequence can also be formed, but ideal ice I without stacking-disorder has never been formed until recently. Here we demonstrate a route to obtain ice I without stacking-disorder by degassing hydrogen from the high-pressure form of hydrogen hydrate, C, which has a host framework isostructural with ice I.
View Article and Find Full Text PDFA high-pressure phase of magnesium chloride hexahydrate (MgCl·6HO-II) and its deuterated counterpart (MgCl·6DO-II) have been identified for the first time by in-situ single-crystal X-ray and powder neutron diffraction. The crystal structure was analyzed by the Rietveld method for the neutron diffraction pattern based on the initial structure determined by single-crystal X-ray diffraction. This high-pressure phase has a similar framework to that in the known ambient-pressure phase, but exhibits some structural changes with symmetry reduction caused by a subtle modification in the hydrogen-bond network around the Mg(HO) octahedra.
View Article and Find Full Text PDFThe methylation of histone H3 at lysine 9 (H3K9me), performed by the methyltransferase Clr4/SUV39H, is a key event in heterochromatin assembly. In fission yeast, Clr4, together with the ubiquitin E3 ligase Cul4, forms the Clr4 methyltransferase complex (CLRC), whose physiological targets and biological role are currently unclear. Here, we show that CLRC-dependent H3 ubiquitylation regulates Clr4's methyltransferase activity.
View Article and Find Full Text PDFPost-translational histone modifications are major regulators of gene expression. However, conventional immunoassays do not provide sufficient information regarding their spatial and temporal dynamic changes. Fluorescence/Förster resonance energy transfer (FRET)-based probes are capable of monitoring the dynamic changes associated with histone modifications in real-time by measuring the balance between histone-modifying enzyme activities.
View Article and Find Full Text PDFThe HTML and PDF versions of this Article were updated after publication to remove images of one individual from Figure 1.
View Article and Find Full Text PDFThe original version of this Article contained an error in the spelling of the author Laurence Faivre, which was incorrectly given as Laurence Faive. This has now been corrected in both the PDF and HTML versions of the Article.
View Article and Find Full Text PDFHeterochromatin protein 1 (HP1) is an evolutionarily conserved chromosomal protein that plays a crucial role in heterochromatin-mediated gene silencing. We previously showed that mammalian HP1α is constitutively phosphorylated at its N-terminal serine residues by casein kinase II (CK2), and that this phosphorylation enhances HP1α's binding specificity for nucleosomes containing lysine 9-methylated histone H3 (H3K9me). Although the presence of additional HP1α phosphorylation during mitosis was reported more than a decade ago, its biological significance remains largely elusive.
View Article and Find Full Text PDFChromatin remodeling is of crucial importance during brain development. Pathogenic alterations of several chromatin remodeling ATPases have been implicated in neurodevelopmental disorders. We describe an index case with a de novo missense mutation in CHD3, identified during whole genome sequencing of a cohort of children with rare speech disorders.
View Article and Find Full Text PDFHistone variants are key epigenetic players that regulate transcription, repair, replication, and recombination of genomic DNA. Histone variant incorporation into nucleosomes induces structural diversity of nucleosomes, consequently leading to the structural versatility of chromatin. Such chromatin diversity created by histone variants may play a central role in the epigenetic regulation of genes.
View Article and Find Full Text PDFPioneer transcription factors specifically target their recognition DNA sequences within nucleosomes. FoxA is the pioneer transcription factor that binds to the gene enhancer in liver precursor cells, and is required for liver differentiation in embryos. The enhancer DNA sequence is reportedly incorporated into nucleosomes in cells, although the nucleosome structure containing the targeting sites for FoxA has not been clarified yet.
View Article and Find Full Text PDF