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Histone Proteins (histone + protein)
Selected AbstractsSyndromes of disordered chromatin remodelingCLINICAL GENETICS, Issue 2 2003J Ausió Syndromes of disordered ,chromatin remodeling' are unique in medicine because they arise from a general deregulation of DNA transcription caused by mutations in genes encoding enzymes which mediate changes in chromatin structure. Chromatin is the packaged form of DNA in the eukaryotic cell. It consists almost entirely of repeating units, called nucleosomes, in which short segments of DNA are wrapped tightly around a disk-like structure comprising two subunits of each of the histone proteins H2A, H2B, H3 and H4. Histone proteins are covalently modified by a number of different adducts (i.e. acetylation and phosphorylation) that regulate the tightness of the DNA,histone interactions. Mutations in genes encoding enzymes that mediate chromatin structure can result in a loss of proper regulation of chromatin structure, which in turn can result in deregulation of gene transcription and inappropriate protein expression. In this review we present examples of representative genetic diseases that arise as a consequence of disordered chromatin remodeling. These include: ,-thalassemia/mental retardation syndrome, X-linked (ATR,X); Rett syndrome (RS); immunodeficiency-centromeric instability,facial anomalies syndrome (ICF); Rubinstein,Taybi syndrome (RSTS); and Coffin,Lowry syndrome (CLS). [source] Modeling H3 histone N-terminal tail and linker DNA interactionsBIOPOLYMERS, Issue 2 2006Giovanni La Penna Abstract Molecular dynamics computer simulations were performed for the 25-residue N-terminal tail of the H3 histone protein in the proximity of a DNA segment of 10 base pairs (bp), representing a model for the linker DNA in chromatin. Several least biased configurations were used as initial configurations. The secondary structure content of the protein was increased by the presence of DNA close to it, but the locations of the secondary motifs were different for different initial orientations of the DNA grooves with respect to the protein. As a common feature to all simulations, the electrostatic attraction between negatively charged DNA and positively charged protein was screened by the water solvent and counterbalanced by the intrinsic compaction of the protein due to hydrophobic effects. The protein secondary structure limited the covering of DNA by the protein to 4,5 bp. The degree of compaction and charge density of the bound protein suggests a possible role of H3 tail in a nonspecific bending and plasticity of the linker DNA when the protein is located in the crowded dense chromatin. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 135,147, 2006 This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Haploinsufficiency and acquired loss of Bcl11b and H2AX induces blast crisis of chronic myelogenous leukemia in a transgenic mouse modelCANCER SCIENCE, Issue 7 2009Akiko Nagamachi Chronic myelogenous leukemia (CML) is a hematological malignancy that begins as indolent chronic phase (CP) but inevitably progresses to fatal blast crisis (BC). p210BCR/ABL, a chimeric protein with enhanced kinase activity, initiates CML CP, and additional genetic alterations account for progression to BC, but the precise mechanisms underlying disease evolution are not fully understood. In the present study, we investigated the possible contribution of dysfunction of Bcl11b, a zinc-finger protein required for thymocyte differentiation, and of H2AX, a histone protein involved in DNA repair, to the transition from CML CP to BC. For this purpose, we crossed CML CP-exhibiting p210BCR/ABL transgenic (BAtg/,) mice with Bcl11b heterozygous (Bcl11b+/,) mice and H2AX heterozygous (H2AX+/,) mice. Interestingly, p210BCR/ABL transgenic, Bcl11b heterozygous (BAtg/,Bcl11b+/,) mice and p210BCR/ABL transgenic, H2AX heterozygous (BAtg/,H2AX+/,) mice frequently developed CML BC with T-cell phenotype and died in a short period. In addition, whereas p210BCR/ABL was expressed in all of the leukemic tissues, the expression of Bcl11b and H2AX was undetectable in several tumors, which was attributed to the loss of the residual normal allele or the lack of mRNA expression. These results indicate that Bcl11b and H2AX function as tumor suppressor and that haploinsufficiency and acquired loss of these gene products cooperate with p210BCR/ABL to develop CML BC. (Cancer Sci 2009; 100: 1219,1226) [source] Development of H1e histone linker-specific antibodies by means of synthetic peptidesCHEMICAL BIOLOGY & DRUG DESIGN, Issue 1 2004K. Foulon Abstract:, A large body of data suggests that the linker histones family (H1) affects gene expression. Investigation of the linker histones role is then of a major interest in cell cycle studies with implications in gene therapy. Indeed, it has been shown that in most tissues a switch of histone subtypes occurs when the cells cease to divide. To investigate linker histone role in gene or transgene expression, an antibody against subtypes of H1 would be useful for immunoprecipitation experiments and further assays measuring H1subtypes,DNA interactions in living cells. In order to produce an antibody against the H1e subtype of linker histones, two synthetic peptides derived from two regions of the H1e mouse histone protein were examined for their potential, [as keyhole limpet hemocyanin (KLH) conjugates] to elicit polyclonal anti-H1e antibodies in New Zealand white rabbits. Selection of the peptide sequences was based on amino acid differences within the different classes of histones and between mice and rabbit histones as well. The evaluation of their potential immunogenic properties was based on examination of peptide hydropathy using predicting algorithms. Immunoglobulins (IgG) obtained from immunized and nonimmunized rabbits were tested using enzyme-linked immunosorbent assay (ELISA) procedures, Western immunoblot, and immunofluorescence experiments. Results showed that the selected synthetic peptides gave rise to a high-titer polyclonal antibody able to recognize the H1e histone under various conditions. This polyclonal antibody did not cross-react with other histones. To our knowledge, this is the first antibody produced against the mouse H1e linker histone. [source] A challenge for regenerative medicine: Proper genetic programming, not cellular mimicryDEVELOPMENTAL DYNAMICS, Issue 12 2007Angie Rizzino Abstract Recent progress in stem cell biology and the reprogramming of somatic cells to a pluripotent phenotype has generated a new wave of excitement in regenerative medicine. Nonetheless, efforts aimed at understanding transdifferentiation, dedifferentiation, and the plasticity of cells, as well as the ability of somatic cells to be reprogrammed, has raised as many questions as those that have been answered. This review proffers the argument that many reports of transdifferentiation, dedifferentiation, and unexpected stem cell plasticity may be due to aberrant processes that lead to cellular look-alikes (cellular mimicry). In most cases, cellular look-alikes can now be identified readily by monitoring gene expression profiles, as well as epigenetic modifications of DNA and histone proteins of the cells involved. This review further argues that progress in regenerative medicine will be significantly hampered by failing to address the issue of cellular look-alikes. Developmental Dynamics 236:3199,3207, 2007. © 2007 Wiley-Liss, Inc. [source] Epigenetic control of plant immunityMOLECULAR PLANT PATHOLOGY, Issue 4 2010MARÍA E. ALVAREZ SUMMARY In eukaryotic genomes, gene expression and DNA recombination are affected by structural chromatin traits. Chromatin structure is shaped by the activity of enzymes that either introduce covalent modifications in DNA and histone proteins or use energy from ATP to disrupt histone,DNA interactions. The genomic ,marks' that are generated by covalent modifications of histones and DNA, or by the deposition of histone variants, are susceptible to being altered in response to stress. Recent evidence has suggested that proteins generating these epigenetic marks play crucial roles in the defence against pathogens. Histone deacetylases are involved in the activation of jasmonic acid- and ethylene-sensitive defence mechanisms. ATP-dependent chromatin remodellers mediate the constitutive repression of the salicylic acid-dependent pathway, whereas histone methylation at the WRKY70 gene promoter affects the activation of this pathway. Interestingly, bacterial-infected tissues show a net reduction in DNA methylation, which may affect the disease resistance genes responsible for the surveillance against pathogens. As some epigenetic marks can be erased or maintained and transmitted to offspring, epigenetic mechanisms may provide plasticity for the dynamic control of emerging pathogens without the generation of genomic lesions. [source] Visible Light Irradiation of Ethidium Bromide,stained Interphase Nuclei Causes DNA,Protein Linking and Structural Stabilization of Nucleoprotein Complexes,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2003Andrey N. Prusov ABSTRACT Fixation of DNA and proteins in the isolated rat hepatocyte nuclei stained with ethidium bromide and irradiated with visible light was analyzed in this study. It was shown that irradiation results in the following modifications of higher-level nucleoprotein complexes of interphase chromatin: (1) the complexes acquire resistance to decondensing treatments, which may be indicative of the formation of links between proteins or proteins and DNA in the chromatin; (2) the linking rate for both DNA and proteins is dose dependent; (3) the irradiation induces intermolecular link formation between DNA molecules, which brings about an increase in the average molecular weight of DNA fragments; (4) some modifications (dimerization, etc.) of histones and nonhistone proteins occur; and (5) histone proteins are not effectively cross-linked to DNA. The structural stabilization of interphase chromatin is possibly mediated by free radical,based mechanisms, whereas disulfide bonds seem to play no significant role in the cross-linking. [source] Flavonoids in plant nuclei: detection by laser microdissection and pressure catapulting (LMPC), in vivo staining, and uv,visible spectroscopic titrationPHYSIOLOGIA PLANTARUM, Issue 1 2006Jürgen Polster Previous studies in our laboratory have indicated that the nuclei of a number of trees are associated with flavonoids, especially flavan-3-ols. In the present study, three techniques were applied to verify that flavonoids are naturally incorporated into nuclei. These were histochemistry, UV,visible (UV-VIS) titration and laser microdissection. Nuclei from intact seed wings of Tsuga canadensis were isolated from their cells using laser microdissection and pressure catapulting (LMPC). Thereafter, the excised nuclei were stained with p -dimethylamino-cinnamaldehyde (DMACA), which resulted in a blue coloration due to the presence of flavanols. Thus, there is no doubt that the nuclei were, prior to staining, associated with flavanols. The nuclei of the coniferous species Abies lasiocarpa, Cedrus deodara, Cedrus libani, Juniperus communis, Picea abies, Picea orientalis and Pseudotsuga menziessii(Douglas fir) showed a yellow fluorescence typical for flavonols from the beginning of bud break over the entire growing season. However, after the bud-breaking period, the nuclei of all species, except for Cedrus deodara, showed additionally a blue reaction for flavanols. Rather late, in midsummer, blue-stained flavanols in nuclei were found in Picea orientalis. Generally, zeatin intensified the flavanol association with the nuclei. The main components of nucleosomes are DNA and the histone proteins. The nature of their association with the flavonols quercetin and rutin was investigated by UV-VIS spectroscopic titration. The data were evaluated by means of the Mauser (A and AD) diagrams. The results indicate that DNA shows largely no spectroscopically detectable association equilibria under the experimental conditions chosen. However, association (aggregation) equilibria can be observed with rutin or quercetin and histone sulphate in Tris buffer (pH 8.0, 7.4 and 7.0). In phosphate buffer, rutin shows spectroscopically no or only weak association with histone sulphate, in contrast to its behaviour towards quercetin. [source] Proteomic profiling of tumor cells after induction of telomere dysfunctionPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 3 2009Stefan Zimmermann Dr. Abstract Cell division in the absence of telomerase causes progressive telomere shortening which ultimately leads to telomere dysfunction and initiation of genome instability. In order to identify factors related to loss of telomere function, the effects of telomerase inhibition on the proteome of five tumor cell lines were followed by SELDI-TOF-MS. Five differentially expressed protein peaks (p<0.01) were found in a total of 60 clones of five cell lines representing four tissues (lung, breast, prostate, and colon) in which telomerase was inhibited by retroviral overexpression of a dominant negative (DN) mutant of human telomerase reverse transcriptase (hTERT). Among these, a 11.3,kDa peak diminished in DN-hTERT clones was identified as histone H4 by nanoflow-HPLC-MS/MS. Immunoblot analysis not only confirmed the decline of histone H4, but also of other core histone proteins including histone H3. Furthermore, upregulation of several cytokeratins was found to be associated with telomere attrition. In conclusion, loss of telomere function is associated with alterations in the proteome which may represent novel biomarkers for the detection of replicative senescence. [source] Recombinant mussel adhesive protein as a gene delivery materialBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2009Dong Soo Hwang Abstract Efficient target gene delivery into eukaryotic cells is important for biotechnological research and gene therapy. Gene delivery based on proteins, including histones, has recently emerged as a powerful non-viral DNA transfer technique. Here, we investigated the potential use of a recombinant mussel adhesive protein, hybrid fp-151, as a gene delivery material, in view of its similar basic amino acid composition to histone proteins, and cost-effective and high-level production in Escherichia coli. After confirming DNA binding affinity, we transfected mammalian cells (human 293T and mouse NIH/3T3) with foreign genes using hybrid fp-151 as the gene delivery carrier. Hybrid fp-151 displayed comparable transfection efficiency in both mammalian cell lines, compared to the widely used transfection agent, LipofectamineÔ 2000. Our results indicate that this mussel adhesive protein may be used as a potential protein-based gene-transfer mediator. Biotechnol. Bioeng. 2009;102: 616,623. © 2008 Wiley Periodicals, Inc. [source] Effects of Chain Length and N-Methylation on a Cation,, Interaction in a ,-Hairpin PeptideCHEMISTRY - A EUROPEAN JOURNAL, Issue 20 2007Robert Abstract The effects of N-methylation and chain length on a cation,, interaction have been investigated within the context of a ,-hairpin peptide. Significant enhancement of the interaction and structural stabilization of the hairpin have been observed upon Lys methylation. Thermodynamic analysis indicates an increased entropic driving force for folding upon methylation of Lys residues. Comparison of lysine to analogues ornithine (Orn) and diaminobutyric acid (Dab) indicates that lysine provides the strongest cation,, interaction and also provides the most stable ,-hairpin due to a combination of side chain,side chain interactions and ,-sheet propensities. These studies have significance for the recognition of methylated lysine in histone proteins. [source] | |||||||||||||