Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chromatin core particle DNA conformation deduced in broad outline by Finch et al. [Finch, J. T., Lutter, L. C., Rhodes, D., Brown, R. S., Rushton, B., Levitt, M. & Klug, A. (1977) Nature 269, 29-36] can be described in detail using other available experimental results. Histone binding sites compatible with the pattern of pancreatic DNase I digestion (Simpson, R. T. & Whitlock, J. P., Jr. (1976) Cell 9, 347-353; Noll, M. (1977) J. Mol. Biol. 116, 49-71; Lutter, L. C. (1977) J. Mol. Biol. 117, 53-69] lend to core particle DNA pseudosymmetry characteristic of molecular point group D(3). DNA symmetry and pseudosymmetry, in turn, imply equivalence and quasi-equivalence properties of the histone packing arrangement that support the following deductions: (i) One and only one alpha(2)beta(2) histone tetramer, presumably (H3)(2)(H4)(2), can serve as a stable subassembly within the histone octamer. (ii) There is a unique, strand-specific way to assign DNA binding domains to the arginine-rich histones (H3 and H4). (iii) Histones H3 and H4 alone should suffice to impose a supercoiled structure on DNA, as is observed experimentally, because only the tetramer can mimic a screw dislocation and thereby complement the screw symmetry of the DNA supercoil. (iv) The two slightly lysine-rich histones H2A and H2B are probably responsible, each in a different way, for dividing the eukaryotic chromatin fiber into discrete subunits. (v) The proposed arrangement of four distinct proteins appears to be a minimum formal requirement for making nucleosomes; that is, for introducing regularly spaced supercoiled DNA folds without also allowing formation of an indefinitely long (and genetically inert) DNA superhelix.
 ...
PMID:Histone packing in the nucleosome core particle of chromatin. 27 80

Transcriptionally active macronuclei and transcriptionally inert micronuclei of the ciliated protozoan Tetrahymena thermophila contain similar DNA sequences but have very different histones associated with the linker regions of chromatin. In situ hybridization showed that a gene coding for micronuclear linker histone is expressed only in association with micronuclear DNA replication, whereas the gene for macronuclear H1 histone is expressed during macronuclear (but not during micronuclear) S phase. These results indicate that cell-cycle regulation plays an important role in directing proteins to the appropriate nucleus in Tetrahymena and that the replication-expression model [Gottesfeld, J. & Bloomer, L. S. (1982) Cell 28, 781-791; Wormington, W. M., Schlissel, M. & Brown, D. D. (1983) Cold Spring Harbor Symp. Quant. Biol. 47, 879-884] for establishing appropriate transcriptionally active or repressed chromatin complexes during DNA replication is generally applicable.
 ...
PMID:Cell-cycle regulation as a mechanism for targeting proteins to specific DNA sequences in Tetrahymena thermophila. 335 76

Systemic lupus erythematosus (SLE) is characterised by the production of a variety of autoantibodies against cell surface, nuclear and cytoplasmic antigens. The antigen or antigens responsible for the induction of this disease is/are unknown. We have analysed the antigenicity and pathogenicity of free histones and histones complexed with RNA in Balb/c, B10 Br, C57BL/6 and MRL-lpr/lpr mice by giving 1 microgram and 25 micrograms of each antigen intraperitoneally in complete and incomplete Freund's adjuvant. The same number of control animals were injected with either adjuvant or PBS. In the initial experiment we gave three doses of antigen at three weekly intervals. B10 Brown and C57BL/6 mice had no response to the antigens. Balb/c mice developed a mild transient antibody response against H1 histone, branched peptide of ubiquitinated H2A (peptide T4) and also against ssDNA. However in repeated experiments when the histone-RNA complex was injected into young MRL-lpr/lpr animals at two weekly intervals, a significantly increased antibody response was detected against H1, peptide T4 and some histone peptide residues (204-218 of H1, 1-20 and 65-85 of H2A, 1-25 of H2B, 1-21 of H3 and 1-29 of H4) compared to the control groups. Moreover, this group also showed elevated serum anti-DNA antibody levels and early impairment of renal function assessed by the urine protein levels. These experiments have demonstrated that there is a genetic variation in antibody responses against histones and histone-RNA complexes and that histone-RNA complexes exaggerate the disease in young MRL-lpr/lpr mice by inducing antibodies to basic regions of histones and other autoantigens.
 ...
PMID:Effect of histone and histone-RNA complexes on the disease process of murine systemic lupus erythematosus. 867 99

Apoptosis has been associated with several events in solid organ transplantation, including ischemia/reperfusion (IR) injury and acute rejection. To determine whether apoptosis-profiles may distinguish these two conditions, we analyzed apoptosis rates in a rat orthotopic small bowel transplant (SBT) model. SBT was performed in Lewis rats with either freshly harvested or preserved (4 h, in UW at 4 degrees C) syngeneic and allogeneic (Brown-Norway) grafts. Bowel samples were collected 2 h after reperfusion and on small bowel transplant postoperative days (POD) 1, 4, and 7. Apoptosis was detected by measuring levels of histone-associated DNA fragments and caspase 3 expression, and by determining apoptotic body counts. All markers measured 2 h after reperfusion increased profoundly in association with preservation. After a significant decrease on POD 1, apoptosis rates rose again between POD 4 and 7 only in allogeneic grafts. This distinct second increase in apoptosis may be an early and specific sign of acute rejection.
 ...
PMID:Increased apoptosis is specific for acute rejection in rat small bowel transplant. 1512 82

[(3)H]luteolin covalently labels two forms (11kDa and 35kDa proteins) of type II binding sites in rat uterine nuclear extracts [K. Shoulars, T. Brown, M. Alejandro, J. Crowley, B. Markaverich, Identification of rat uterine nuclear type II [(3)H]estradiol binding sites as histone H4, Biochem. Biophys. Res. Commun. 296 (2002) 1083-1090]. The 11kDa protein was identified as histone H4. Levels of the 35kDa protein were insufficient for sequencing; however, this protein was recognized by anti-histone H4 antibodies. Histones H3 and H4 exist as dimers in vivo (mw>>35kDa) and we suspected the 35kDa [(3)H]luteolin-labeled protein in uterine nuclear extracts might be a complex of histones H3 and H4. This manuscript describes methods for the purification of commercially available calf thymus core histones that retain [(3)H]luteolin binding activity and are of sufficient purity for recombination studies. Mixing experiments with pure H3 and H4 from calf thymus demonstrate that a 35kDa H3-H4 dimer capable of binding [(3)H]luteolin is generated and this protein appears equivalent to the 35kDa [(3)H]luteolin binding protein in rat uterine nuclear extracts. If this is the case, type II site ligands including MeHPLA, luteolin, and other bioflavonoids and phytoestrogens may control histone-dependent gene transcription and cellular proliferation via binding to and modulating core histone/nucleosome function.
 ...
PMID:Nuclear type II [3H]estradiol binding sites: a histone H3-H4 complex. 1587 66

Aflatoxin B1 (AFB(1)) is a potent human hepatotoxin and hepatocarcinogen produced by the mold Aspergillus flavus. In human, AFB(1) is bioactivated by cytochrome P450 (CYP450) enzymes, primarily CYP1A2, to the genotoxic epoxide that forms N(7)-guanine DNA adducts. To characterize the transcriptional responses to genotoxic insults from AFB(1), a strain of Saccharomyces cerevisiae engineered to express human CYP1A2 was exposed to doses of AFB(1) that resulted in minimal lethality, but substantial genotoxicity. Flow cytometric analysis demonstrated a dose and time dependent S phase delay under the same treatment conditions, indicating a checkpoint response to DNA damage. Replicate cDNA microarray analyses of AFB(1) treated cells showed that about 200 genes were significantly affected by the exposure. The genes activated by AFB(1)-treatment included RAD51, DUN1 and other members of the DNA damage response signature reported in a previous study with methylmethane sulfonate and ionizing radiation [A.P. Gasch, M. Huang, S. Metzner, D. Botstein, S.J. Elledge, P.O. Brown, Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p, Mol. Biol. Cell 12 (2001) 2987-3003]. However, unlike previous studies using highly cytotoxic doses, environmental stress response genes [A.P. Gasch, P.T. Spellman, C.M. Kao, O. Carmel-Harel, M.B. Eisen, G. Storz, D. Botstein, P.O. Brown, Genomic expression programs in the response of yeast cells to environmental changes, Mol. Biol. Cell 11 (2000) 4241-4257] were largely unaffected by our dosing regimen. About half of the transcripts affected are also known to be cell cycle regulated. The most strongly repressed transcripts were those encoding the histone genes and a group of genes that are cell cycle regulated and peak in M phase and early G1. These include most of the known daughter-specific genes. The rapid and coordinated repression of histones and M/G1-specific transcripts cannot be explained by cell cycle arrest, and suggested that there are additional signaling pathways that directly repress these genes in cells under genotoxic stress.
 ...
PMID:Analysis of cellular responses to aflatoxin B(1) in yeast expressing human cytochrome P450 1A2 using cDNA microarrays. 1612 66

Brown apical necrosis of English walnut and grey necrosis of hazelnut are destructive fruit diseases caused by a complex of opportunistic fungi including several small-spored catenulate Alternaria taxa. Thirty Alternaria isolates recovered from walnut and hazelnut fruit that were pathogenic on their respective host were compared along with type or representative isolates of A. alternata, A. tenuissima, A. arborescens, and A. infectoria using morphological and molecular criteria. Morphological examination using standardized procedures separated the walnut and hazelnut isolates into three morphological groups: the A. alternata group, the A. tenuissima group, and the A. arborescens group based upon common characteristics of the conidium and the sporulation apparatus. To evaluate genetic relationships among these groups, AFLP markers, inter simple sequence repeat (ISSR) markers, and histone gene sequence data were compared. Based upon AFLP data, the A. alternata and A. tenuissima groups comprised a single lineage, and the A. arborescens group comprised a separate lineage. ISSR data supported the grouping by AFLP data except for three isolates of the A. alternata group that clustered with the A. arborescens group. Base substitution of the H4 gene supported the discrimination of the A. arborescens group from the A. alternata and A. tenuissima groups. Tests of hypotheses based upon groupings derived from the various data sets supported the discrimination of the A. arborescens group but did not support the discrimination of the A. alternata group from the A. tenuissima group.
 ...
PMID:Polyphasic classification of Alternaria isolated from hazelnut and walnut fruit in Europe. 1707 26

Successful cloning by somatic cell nuclear transfer (SCNT) is thought to require reprogramming of a somatic nucleus to a state of restored totipotentiality [Dean, W., Santos, F., Reik, W., 2003. Epigenetic programming in early mammalian development and following somatic cell nuclear transfer. Semin. Cell. Dev. Biol. 14, 93-100; Jouneau, A., Renard, J.P., 2003. Reprogramming in nuclear transfer. Curr. Opin. Genet. Dev. 13, 486-491; ]. Though SCNT-induced reprogramming is reminiscent of the reprogramming that occurs after fertilization, reprogramming a differentiated nucleus to an embryonic state is delayed and incomplete in comparison (for review, see ). This is likely due to the existence of an epigenetic-based cellular memory, or program, that serves to regulate global patterns of gene expression, and is the basis of a genome defense mechanism that silences viruses and transposons. The mechanisms of this memory include CpG methylation and modification of histones. Recent evidence by Feng et al. [Feng, Y.-Q., Desprat, R., Fu, H., Olivier, E., Lin, C.M., Lobell, A., Gowda, S.N., Aladjem, M.I., Bouhasira, E.E., 2006. DNA methylation supports intrinsic epigenetic memory in mammalian cells. PLOS Genet. 2, 0461-0470], using a transgenic experimental system, indicates that these marks may be acquired in more than one order and thus, silent heterochromatic structure can be initiated by either methylation of CpG dinucleotides or by histone modifications. In this system, however, CpG methylation appears to differ from histone modifications because it bestows a persistent epigenetic, or cellular, memory. In other words, CpG methylation can independently confer cellular memory, whereas histone modifications appear to be limited in this capacity. Therefore, in the context of genomic reprogramming induced by SCNT, efficient demethylation is likely a key (if not the only) rate-limiting step to improving the efficiency and outcomes of SCNT cloning. This review discusses the possibility of targeting cellular memory, and in particular inducing demethylation of a somatic nucleus prior to nuclear transfer, to enable reprogramming events typically carried out by oocyte factors and thereby improve developmental competence of SCNT-reconstructed embryos. Several recent published reviews of SCNT, cellular reprogramming and genomic demethylation served as valuable sources for the authors and are recommended as supplemental reading. These include the following: Bird, A., 2002. DNA methylation patterns and epigenetic memory. Gen. Dev. 16, 6-21; Grafi, G., 2004. How cells dedifferentiate: a lesson from plants. Dev. Biol. 268, 1-6; Latham, K.E., 2005. Early and delayed aspects of nuclear reprogramming during cloning. Biol. Cell 97, 119-132; Lyko, F., Brown, R., 2005. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J.Natl. Cancer Inst. 97, 1498-1506; Morgan, H.D., Santos, F., Green, K., Dean, W., Reik, W., 2005. Epigenetic reprogramming in mammals. Hum. Mol. Gen. 14, R47-R58; Szyf, M., 2005. DNA methylation and demethylation as targets for anticancer therapy. Biochemistry 70, 533-549; Buszczak, M., Spradling, A.C., 2006. Searching chromatin for stem cell identity. Cell 125, 233-236; Gurdon, J.B., 2006. From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation. Annu. Rev. Cell. Dev. Biol. 22, 1-22; Yoo, C.B., Jones, P.A., 2006. Epigenetic therapy of cancer: past, present and future. Nat. Rev. 5, 37-50.
 ...
PMID:Targeting cellular memory to reprogram the epigenome, restore potential, and improve somatic cell nuclear transfer. 1716 76

N-acetyl-dinaline (CI-994) is an investigational anti-cancer drug which inhibits histone deacetylases. We evaluated the interaction between CI-994 and conventional chemotherapeutics used in acute myeloid leukemia (AML) in a rat model for AML and Brown Norway rat acute myelocytic leukemia (BNML). In vitro, CI-994 in combination with cytarabine (ara-C), daunorubicin and mitoxantrone, resulted in moderate synergism. In vivo, higher dosages of CI-994 induced complete remissions. CI-994/ara-C was very active against BNML. The combinations of CI-994/daunorubicin and CI-994/mitoxantrone were also active against BNML. This study demonstrates favorable in vitro and in vivo interactions between CI-994 and conventional anti-cancer agents used for the treatment of AML.
 ...
PMID:CI-994 (N-acetyl-dinaline) in combination with conventional anti-cancer agents is effective against acute myeloid leukemia in vitro and in vivo. 1849 59

The prevalence of obesity continues to increase particularly in developed countries. To establish the primary mechanisms involved, relevant animal models which track the developmental pathway to obesity are required. This need is emphasized by the substantial rise in the number of overweight and obese children, of which a majority will remain obese through adulthood. The past half century has been accompanied with unprecedented transitions in our lifestyle. Each of these changes substantially contributes to enhancing our capacity to store energy into adipose tissues. The complex etiology of adiposity is critical as a majority of models investigating obesity utilize a simplistic high-fat/low-carbohydrate diet, fed over a short time period to comparatively young inbred animals maintained in fixed environment. The natural history of obesity is much more complex involving many other mechanisms and this type of challenge may not be the optimal experimental intervention. Such processes include changes in adipose tissue composition with time and the transition from brown to white adipose tissue. Brown adipose tissue, due its unique ability to rapidly produce large amounts of heat could have a pivotal role in energy balance and is under epigenetic regulation mediated by the histone H3k9-specific demethylase Jhdma2a. Furthermore, day length has a potential role in determining endocrine and metabolic responses in brown fat. The potential to utilize novel models and interventions across a range of animal species in adipose tissue development may finally start to yield sustainable strategies by which excess fat mass can, at last, be avoided in humans.
 ...
PMID:The obesity epidemic: from the environment to epigenetics - not simply a response to dietary manipulation in a thermoneutral environment. 2230 20


1 2 3 Next >>