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Core Histones (core + histone)
Selected AbstractsGlobal analysis of functional surfaces of core histones with comprehensive point mutantsGENES TO CELLS, Issue 1 2007Kazuko Matsubara The core histones are essential components of the nucleosome that act as global negative regulators of DNA-mediated reactions including transcription, DNA replication and DNA repair. Modified residues in the N-terminal tails are well characterized in transcription, but not in DNA replication and DNA repair. In addition, roles of residues in the core globular domains are not yet well characterized in any DNA-mediated reactions. To comprehensively understand the functional surface(s) of a core histone, we constructed 320 yeast mutant strains, each of which has a point mutation in a core histone, and identified 42 residues responsible for the suppressor of Ty (Spt - ) phenotypes, and 8, 30 and 61 residues for sensitivities to 6-azauracil (6AU), hydroxyurea (HU) and methyl-methanesulfonate (MMS), respectively. In addition to residues that affect one specific assay, residues involved in multiple reactions were found, and surprisingly, about half of them were clustered at either the nucleosome entry site, the surface required for nucleosome,nucleosome interactions in crystal packing or their surroundings. This comprehensive mutation approach was proved to be powerful for identification of the functional surfaces of a core histone in a variety of DNA-mediated reactions and could be an effective strategy for characterizing other evolutionarily conserved hub-like factors for which surface structural information is available. [source] Induction of hepatic differentiation of mouse bone marrow stromal stem cells by the histone deacetylase inhibitor VPAJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Ye Chen Abstract Bone marrow stromal stem cells (BMSSCs) may have potential to differentiate in vitro and in vivo into hepatocytes. Here, we investigated the effects of valproic acid (VPA) involved in epigenetic modification, a direct inhibitor of histone deacetylase, on hepatic differentiation of mouse BMSSCs. Following the treatment of 2.5 mM VPA for 72 hrs, the in vitro expanded, highly purified and functionally active mouse BMSSCs from bone marrow were either exposed to some well-defined cytokines and growth factors in a sequential way (fibroblast growth factor-4 [FGF-4], followed by HGF, and HGF + OSM + ITS + dexamethasone, resembling the order of secretion during liver embryogenesis) or transplanted (caudal vein) in mice submitted to a protocol of chronic injury (chronic i.p. injection of CCl4). Additional exposure of the cells to VPA considerably improved the in vitro differentiation, as demonstrated by a more homogeneous cell population exhibited epithelial morphology, increasing expression of hepatic special genes and enhanced hepatic functions. Further more, in vivo results indicate that the pre-treatment of VPA significantly increased the homing efficiency of BMSSCs to the site of liver injury and, additionally, for supporting hepatic differentiation as well as in vitro. We have demonstrated the usefulness of VPA in the transdifferentiation of BMSSCs into hepatocytes both in vitro and in vivo, and regulation of fibroblast growth factor receptors (FGFRs) and c-Met gene expression through post-translational modification of core histones might be the primary initiating event for these effects. This mode could be helpful for liver engineering and clinical therapy. [source] Growth phase-dependent expression and degradation of histones in the thermophilic archaeon Thermococcus zilligiiMOLECULAR MICROBIOLOGY, Issue 4 2000Marcel E. Dinger HTz is a member of the archaeal histone family. The archaeal histones have primary sequences and structural similarity to the eukaryal histone fold domain, and are thought to resemble the archetypal ancestor of the eukaryal nucleosome core histones. The effects of growth phase on the total soluble proteins from Thermococcus zilligii, isolated after various stages of growth from mid-logarithmic to late stationary phase, were examined by denaturing polyacrylamide gel electrophoresis. On entry into stationary phase, at least 11 proteins were detected that changed considerably in level. One of these proteins was identified by Western hybridization as HTz. The level of HTz decreased dramatically as cells entered stationary phase, and it could not be detected by late stationary phase. Unexpectedly, the Western hybridization detected a second protein, with an estimated molecular mass of approximately 14 kDa, which paralleled the decrease in level of HTz. Native purified HTz was shown to retain complete activity after prolonged incubation at the growth temperature of the organism, suggesting that the decrease in HTz was a specific cell-regulated process. Analysis of native purified HTz by electrospray ionization mass spectrometry revealed the molecular masses of HTz1 and HTz2 to be 7204 ± 3 Da and 7016 ± 3 Da respectively. The only non-covalent species that was detected corresponded to the molecular mass of an HTz1,HTz2 heterodimer. Northern analyses of T. zilligii total RNA with an htz1 gene probe indicated a rapid decrease in expression of htz1 with progression of the growth phase, and complete repression of htz1 transcript synthesis by late logarithmic phase. Three proteins that changed in level with growth phase were identified by N-terminal sequence analysis. The first was homologous to a hypothetical protein conserved in all Archaea sequenced to date, the second to the Sac10b family of archaeal DNA-binding proteins and the third to the C-terminal region of the leucine-responsive regulatory family of DNA-binding proteins (LRPs). [source] Chromatin dynamics of unfolding and refolding controlled by the nucleosome repeat length and the linker and core histonesBIOPOLYMERS, Issue 4 2007Toshiro Kobori Abstract Chromatin is composed of genomic DNA and histones, forming a hierarchical architecture in the nucleus. The chromatin hierarchy is common among eukaryotes despite different intrinsic properties of the genome. To investigate an effect of the differences in genome organization, chromatin unfolding processes were comparatively analyzed using Schizosaccaromyces pombe, Saccharomyces cerevisiae, and chicken erythrocyte. NaCl titration showed dynamic changes of the chromatin. 400,1000 mM NaCl facilitated beads with ,115 nm in diameter in S. pombe chromatin. A similar transition was also observed in S. cerevisiae chromatin. This process did not involve core histone dissociation from the chromatin, and the persistence length after the transition was ,26 nm for S. pombe and ,28 nm for S. cerevisiae, indicating a salt-induced unfolding to "beads-on-a-string" fibers. Reduced salt concentration recovered the original structure, suggesting that electrostatic interaction would regulate this discrete folding-unfolding process. On the other hand, the linker histone was extracted from chicken chromatin at 400 mM NaCl, and AFM observed the "beads-on-a-string" fibers around a nucleus. Unlike yeast chromatin, therefore, this unfolding was irreversible because of linker histone dissociation. These results indicate that the chromatin unfolding and refolding depend on the presence and absence of the linker histone, and the length of the linker DNA. © 2007 Wiley Periodicals, Inc. Biopolymers 85:295,307, 2007. 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] | ||||||||||