Histone methylation plays an important role in eukaryotic transcriptional regulation. A number of histone methyltransferases (HMTases) with distinct functions have been identified. The HSPC069/HYPB gene was originally isolated from the human hematopoietic stem/progenitor cells (HSPCs), and it was also identified as a huntingtin interacting protein, implicated in the pathogenesis of Huntington disease (HD). However, its biochemical function is poorly understood. Here we report the structural and functional characterization of the huntingtin interacting protein B (HYPB). 1) The triplicate AWS-SET-PostSET domains mediate a histone H3 lysine 36 specific HMTase activity. 2) A low charged region that is rich in glutamine and proline has been characterized as a novel transcriptional activation domain. The structural features of this region are evolutionarily conserved in vertebrates. 3) Coimmunoprecipitation assays indicate that HYPB protein associates with hyperphosphorylated RNA polymerase II (RNAPII) but not the unphosphorylated form. Furthermore, the RNAPII-association region of HYPB protein has been identified to encompass the C-terminal 142 amino acids. Thus, our results suggest that HYPB HMTase may coordinate histone methylation and transcriptional regulation in mammals and open perspective for the further study of the potential roles of HYPB protein in hematopoiesis and pathogenesis of HD.Nucleosome, the bead-like unit of DNA packaging in eukaryotic cells, consists of DNA wound around a protein core made up of eight histone molecules. Covalent modifications of the N-terminal tails of the core histones have emerged as key regulatory mechanisms of gene expression (1-3). These histone modifications, including acetylation, phosphorylation, ubiquitination, and methylation, create both synergistic and antagonistic signals that correlate with the transcriptional activity of a gene, through recruiting/dispelling some protein complexes or through changing the structure of chromatin to allow access for RNA polymerase to initiate transcription. Moreover, these histone modifications and the consequent changes in chromatin structure may serve as an epigenetic marking system that is responsible for establishing and maintaining the heritable programs of gene expression during cellular differentiation and organism development (4, 5).Methylations of histone lysine residues, with exception of H3 lysine 79, are catalyzed by a family of SET domain-containing proteins (6). The SET domain is an evolutionarily conserved, ϳ130-amino acid sequence motif. It was originally identified in members of polycomb group (PcG), trithorax group (trxG), and Su(var) genes and was named after the genes Su(var)3-9, Enhancer of zeste (E(z)) and trithorax (trx) (7). Not all SET domain-containing proteins possess histone methyltransferase (HMTase) 5 activities. The cysteine-rich regions adjacent to the SET domains are also required (8,9). In addition to the SET domains, most HMTases carry other functional domains such as transcriptional activation or re...
Material processing is critical for obtaining high-performance solar cells, which influences the morphological, crystal, and electrical properties of the functional materials in a device. Sb 2 (S,Se) 3 can be considered as a quasi-binary compound since sulfur and selenium can be alloyed with a continuous ratio due to the identical crystal structure of Sb 2 S 3 and Sb 2 Se 3 and close ionic radius between sulfur and selenium. [1-3] This simple chemical composition allows for facile synthesis of Sb 2 (S,Se) 3 film with a well-defined crystal structure. In this regard, both
The first and second substitution reactions between activated (hydrolyzed) cisplatin, Pt(NH3)2(H2O)2(2+), and purine bases guanine and adenine are explored using the B3LYP hybrid functional, IEF-PCM solvation models, and large basis sets. The computed free energy barrier for the first substitution is 19.5 kcal/mol for guanine (exptl value = 18.3 kcal/mol) and 24.0 kcal/mol for adenine. The observed predominance toward guanine in the first substitution is explained in terms of significantly larger stabilization energy for the initially formed complex, compared with adenine, in combination with favored kinetics, and represents a revised view of the proposed mechanism for cisplatin binding to DNA. For the second substitution, the computed barrier for Pt(NH3)2G2(2+) head-to-head formation is 22.5 kcal/mol, in very good agreement with experimental data for adduct closure (23.4 kcal/mol). Again, a higher stability in complexation with G over A is ascribed as the main contributing factor favoring G over A substitution. The calculations provide a first explanation for the predominance of 1,2-d(GpG) over 1,2-d(ApG) intrastrand didentate adducts, and the origin of the 5'-3' direction specificity of the 1,2-d(ApG) adducts.
Kesterite-structured quaternary semiconductor Cu2ZnSnS4 (CZTS) has been commonly used as light absorber in thin film solar cells on the basis of its optimal bandgap of 1.5 eV, high absorption coefficient, and earth-abundant elemental constituents. Herein we applied CZTS nanoparticles as a novel inorganic hole transporting material (HTM) for organo-lead halide perovskite solar cells (PSCs) for the first time, achieving a power conversion efficiency (PCE) of 12.75%, which is the highest PCE for PSCs with Cu-based inorganic HTMs reported up to now, and quite comparable to that obtained for PSCs based on commonly used organic HTM such as 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-MeOTAD). The size of CZTS nanoparticles and its incorporation condition as HTM were optimized, and the effects of CZTS HTM on the optical absorption, crystallinity, morphology of the perovskite film and the interface between the perovskite layer and the Au electrode were investigated and compared with the case of spiro-MeOTAD HTM, revealing the role of CZTS in efficient hole transporting from the perovskite layer to the top Au electrode as confirmed by the prohibited charge recombination at the perovskite/Au electrode interface. On the basis of the effectiveness of CZTS as a low-cost HTM competitive to spiro-MeOTAD in PSCs, we demonstrate the new role of CZTS in photovoltaics as a hole conductor beyond the traditional light absorber.
Chalcopyrite compound CuGaTe2 is the focus of much research interest due to its high power factor. However, its high intrinsic lattice thermal conductivity seriously impedes the promotion of its thermoelectric performance. Here, it is shown that through alloying of isoelectronic elements In and Ag in CuGaTe2, a quinary alloy compound system Cu1−xAgxGa0.4In0.6Te2 (0 ≤ x ≤ 0.4) with complex nanosized strain domain structure is prepared. Due to strong phonon scattering mainly by this domain structure, thermal conductivity (at 300 K) drops from 6.1 W m−1 K−1 for the host compound to 1.5 W m−1 K−1 for the sample with x = 0.4. As a result, the optimized chalcopyrite sample Cu0.7Ag0.3Ga0.4In0.6Te2 presents an outstanding performance, with record‐high figure of merit (ZT) reaching 1.64 (at 873 K) and average ZT reaching 0.73 (between ≈300 and 873 K), which are ≈37 and ≈35% larger than the corresponding values for pristine CuGaTe2, respectively, demonstrating that such domain structure arising from isoelectronic multielement alloying in chalcopyrite compound can effectively suppress its thermal conductivity and elevate its thermoelectric performance remarkably.
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