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RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination
Matthews, Adam G. W.,Kuo, Alex J.,Ramó,n-Maiques, Santiago,Han, Sunmi,Champagne, Karen S.,Ivanov, Dmitri,Gallardo, Mercedes,Carney, Dylan,Cheung, Peggie,Ciccone, David N.,Walter, Kay L.,Utz, Pau Nature Publishing Group 2007 Nature Vol.450 No.7172
Nuclear processes such as transcription, DNA replication and recombination are dynamically regulated by chromatin structure. Eukaryotic transcription is known to be regulated by chromatin-associated proteins containing conserved protein domains that specifically recognize distinct covalent post-translational modifications on histones. However, it has been unclear whether similar mechanisms are involved in mammalian DNA recombination. Here we show that RAG2—an essential component of the RAG1/2 V(D)J recombinase, which mediates antigen-receptor gene assembly—contains a plant homeodomain (PHD) finger that specifically recognizes histone H3 trimethylated at lysine 4 (H3K4me3). The high-resolution crystal structure of the mouse RAG2 PHD finger bound to H3K4me3 reveals the molecular basis of H3K4me3-recognition by RAG2. Mutations that abrogate RAG2’s recognition of H3K4me3 severely impair V(D)J recombination in vivo. Reducing the level of H3K4me3 similarly leads to a decrease in V(D)J recombination in vivo. Notably, a conserved tryptophan residue (W453) that constitutes a key structural component of the K4me3-binding surface and is essential for RAG2’s recognition of H3K4me3 is mutated in patients with immunodeficiency syndromes. Together, our results identify a new function for histone methylation in mammalian DNA recombination. Furthermore, our results provide the first evidence indicating that disrupting the read-out of histone modifications can cause an inherited human disease.
Josephson Current in Strongly Correlated Double Quantum Dots
Ž,itko, Rok,Lee, Minchul,Ló,pez, Rosa,Aguado, Ramó,n,Choi, Mahn-Soo American Physical Society 2010 Physical Review Letters Vol.105 No.11
<P>We study the Josephson current through a serial double quantum dot and the associated 0-? transitions which result from the subtle interplay between the superconductivity, the Kondo physics, and the interdot superexchange interaction. The competition between them is examined by tuning the relative strength ?/T(K) of the superconducting gap and the Kondo temperature, for different strengths of the superexchange coupling determined by the interdot tunneling t relative to the level broadening ?. We find strong renormalization of t, a significant role of the superexchange coupling J, and a rich phase diagram of the 0 and ?-junction regimes. In particular, when both the superconductivity and the exchange interaction compete with the Kondo physics (???(K)), there appears an island of ?' phase at large values of the superconducting phase difference.</P>
Cleto Alvarez-Aguilar,Maria Lucia Enrí,quez-Ramí,rez,Benigno Figueroa-Nuñ,ez,Anel Gó,mez-Garcí,a,Ernesto Rodrí,guez-Ayala,Cristina Morá,n-Moguel,Victor Manuel 생화학분자생물학회 2007 Experimental and molecular medicine Vol.39 No.3
Metabolic Syndrome (MS) is recognized as a cluster of cardiovascular risk factors. All components of MS have a genetic base. Genes of the renin angiotensin system are potential candidate genes for MS. We investigated whether angiotensin converting en-zyme (ACE) gene polymorphism increases suscep-tibility to MS as an entity in a Mexican population. In a cross-sectional study, 514 individuals were studied including 245 patients with MS and 269 subjects without MS criteria. ACE gene polymorphism was detected using PCR. MS was defined according to The National Cholesterol Education Program Expert Blood Cholesterol in Adults (Adult Treatment Panel III) criteria, except that the raised fasting plasma glucose ≥100 mg/dl criterion for identification of intolerance fasting glucose was modified in accordance with the suggestion of the American Diabetes Association. Patients with MS were sig - nificantly different from subjects without MS in relation to mean body mass index (BMI), waist circumference (WC), systolic blood pressure, diastolic blood pressure, glucose, total cholesterol (C), triglycerides, HDL-C, and LDL-C (P<0.0001). The differences in the mean BMI, WC, glucose, total cholesterol, triglycerides, LDL-C, and HDL-C were maintained in patients with the MS and DD genotypes (P<0.01). The DD genotype was strongly asso - ciated with MS (adjusted OR = 5.48, 95% CI 3.20-9.38, P<0.0001). We concluded that the DD genotype increases susceptibility to MS in a Mexican pop - ulation. These results indicate that pharmacological and non-pharmacological treatment and a reduction in body fat will have important therapeutic im - plications in this disease.
Li, Xiaoe,Nazeeruddin, Mohammad K.,Thelakkat, Mukundan,Barnes, Piers R. F.,Vilar, Ramó,n,Durrant, James R. The Royal Society of Chemistry 2011 Physical chemistry chemical physics Vol.13 No.4
<P>We report the application of spectroelectrochemical techniques to compare the hole percolation dynamics of molecular networks of two ruthenium bipyridyl complexes adsorbed onto mesoporous, nanocrystalline TiO<SUB>2</SUB> films. The percolation dynamics of the ruthenium complex <I>cis</I>-di(thiocyanato)(2,2′-bipyridyl-4,4′-dicarboxylic acid)-(2,2′-bipyridyl-4,4′-tridecyl) ruthenium(<SMALL>II</SMALL>), N621, is compared with those observed for an analogous dye with an additional tri-phenyl amine (TPA) donor moiety, <I>cis</I>-di(thiocyanato)(2,2′-bipyridyl-4,4′-dicarboxylic acid)-(2,2′-bipyridyl-4,4′-bis(vinyltriphenylamine)) ruthenium(<SMALL>II</SMALL>), HW456. The <I>in situ</I>oxidation of these ruthenium complexes adsorbed to the TiO<SUB>2</SUB> films is monitored by cyclic voltammetry and voltabsorptometry, whilst the dynamics of hole (cation) percolation between adsorbed ruthenium complexes is monitored by potentiometric spectroelectrochemistry and chronoabsorptometry. The hole diffusion coefficient, <I>D</I><SUB>eff</SUB>, is shown to be dependent on the dye loading on the nanocrystalline TiO<SUB>2</SUB> film, with a threshold observed at ∼60% monolayer surface coverage for both dyes. The hole diffusion coefficient of HW456 is estimated to be 2.6 × 10<SUP>−8</SUP> cm<SUP>2</SUP>/s, 20-fold higher than that obtained for the control N621, attributed to stronger electronic coupling between the TPA moieties of HW456 accelerating the hole percolation dynamics. The presence of mercuric ions, previously shown to bind to the thiocyanates of analogous ruthenium complexes, resulted in a quenching of the hole percolation for N621/TiO<SUB>2</SUB> films and an enhancement for HW456/TiO<SUB>2</SUB> films. These results strongly suggest that the hole percolation pathway is along the overlapped neighbouring -NCS groups for the N621 molecules, whereas in HW456 molecules cation percolation proceeds between intermolecular TPA ligands. These results are discussed in the context of their relevance to the process of dyeregeneration in dye sensitised solar cells, and to the molecular wiring of wide bandgap inorganic materials for battery and sensing applications.</P> <P>Graphic Abstract</P><P>We employ spectroelectrochemical techniques to compare the hole percolation dynamics of two ruthenium bipyridyl complexes adsorbed onto mesoporous TiO<SUB>2</SUB> films. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c0cp01013h'> </P>