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  • Journal article
    Ito K, J Barnes P, M Adcock I, 2000,

    Histone acetylation and deacetylation.

    , Methods Mol Med, Vol: 44, Pages: 309-319, ISSN: 1543-1894

    In the resting cell, DNA is tightly compacted to prevent transcription factor accessibility. During activation of the cell, this compact inaccessible DNA is made available to DNA-binding proteins, thus allowing the induction of gene transcription (1 ,2). DNA is packaged into chromatin, a highly organized and dynamic protein-DNA complex. The fundamental subunit of chromatin, the nucleosome, is composed of an octomer of four core histones, an H3/H4 tetramer and two H2A/H2B dimers, surrounded by 146 bp DNA (2,3). The packaging of DNA into nucleosomes acts as a barrier to the initiation of transcription by preventing the access of transcriptional factors, and RNA polymerase II, to their cognate recognition sequences (4). Specific lysine residues in the N-terminal tails of the core histone can be post-translationally modified by acetylation of the ε-amino group. The dynamic equilibrium of core histone acetylation is established and maintained by histone acetyltransferase (HAT) and histone deacetylase (HDAC). Several transcriptional regulators possess intrinsic HAT and HDAC activities, strongly suggesting that histone acetylation and deacetylation play a causal role in regulating transcription (5-8). There is compelling evidence that increased gene transcription is associated with an increase in histone acetylation; hypoacetylation of histone is correlated with reduced transcription or gene silencing (2 ,7,8; Fig 1).
  • Conference paper
    Byrne B, Jormakka M, Abramson J, Iwata Set al., 2000,

    A novel, fusion protein strategy for membrane protein crystallisation.

    , Publisher: INT UNION CRYSTALLOGRAPHY, Pages: S58-S58, ISSN: 2053-2733
  • Journal article
    Negrete-Urtasun S, Reiter W, Diez E, Denison SH, Tilburn J, Espeso EA, Peñalva MA, Arst HNet al., 1999,

    Ambient pH signal transduction in <i>Aspergillus</i>:: completion of gene characterization (vol 33, pg 994, 1999)

    , MOLECULAR MICROBIOLOGY, Vol: 34, Pages: 1149-1149, ISSN: 0950-382X
  • Journal article
    Byrne B, McGregor A, Taylor PL, Sellar R, Rodger FE, Fraser HM, Eidne KAet al., 1999,

    Isolation and characterisation of the marmoset gonadotrophin releasing hormone receptor:: Ser<SUP>140</SUP> of the DRS motif is substituted by Phe

    , JOURNAL OF ENDOCRINOLOGY, Vol: 163, Pages: 447-456, ISSN: 0022-0795
  • Journal article
    Moffatt MF, Cookson WO, 1999,

    Genetics of asthma and inflammation: the status.

    , Curr Opin Immunol, Vol: 11, Pages: 606-609, ISSN: 0952-7915

    Genome-wide screens are consistently finding linkage between asthma-associated traits and specific chromosomal loci. Several loci coincide with linkages to other inflammatory diseases, suggesting the presence of common pathways in their pathogenesis. Candidate-gene studies have found an association between a CD14 polymorphism and IgE levels, suggesting a mechanism for the increased prevalence of allergic disease. A polymorphism in Fc epsilon RI-beta shows parent-of-origin effects when associated with severe infantile eczema, further illustrating the complexity of gene-environment effects on the developing immune system.
  • Journal article
    Cookson W, 1999,

    The alliance of genes and environment in asthma and allergy.

    , Nature, Vol: 402, Pages: B5-11, ISSN: 0028-0836

    The diseases of asthma, eczema and hay fever are typified by reactions to common allergens, which are mediated by immunoglobulin E. These allergic diseases are increasing in prevalence, and are now a major source of disability throughout the developed world. They are the result of complex interactions between largely unknown genetic and environmental mechanisms. The identification of the environmental factors offers the real possibility of prevention of disease, and unravelling the genetics of allergic illnesses is likely to change their classification and treatment. Early life seems particularly important, when the initiation of allergic disease may result from genetic and environmental modification of the immune interaction between mother and child.
  • Journal article
    Palmer LJ, Rye PJ, Gibson NA, Moffatt MF, Goldblatt J, Burton PR, Cookson WO, Lesouëf PNet al., 1999,

    Association of FcepsilonR1-beta polymorphisms with asthma and associated traits in Australian asthmatic families.

    , Clin Exp Allergy, Vol: 29, Pages: 1555-1562, ISSN: 0954-7894

    BACKGROUND: Asthma is a genetically complex disease, and is characterized by elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts and increased airway responsiveness. Polymorphisms in the beta subunit of the high affinity receptor for IgE (FcepsilonR1-beta) have been previously associated with these phenotypes and with an increased risk of asthma. OBJECTIVE: To investigate the association of all known bi-allelic polymorphisms in FcepsilonR1-beta to asthma and quantitative traits associated with asthma in a selected sample of Australian asthmatic children and their nuclear families. METHODS: Australian Caucasian nuclear families (n = 134 subjects) were recruited on the basis of a child proband with current, severe, symptomatic asthma. The quantitative traits assessed included serum levels of total IgE and specific IgE to house dust mite and mixed grass, blood eosinophil counts and the dose-response slope of the forced expiratory volume in 1 s to histamine provocation. RESULTS: Neither the Leu181 nor the E237G mutations were detected in this population. Allele B of RsaI intron 2 (RsaI_in2*B) was significantly associated with physician-diagnosed asthma (ever) (P = 0.002). Alleles of both the RsaI_in2 and RsaI exon 7 (RsaI_ex7) polymorphisms were significantly associated with loge total serum IgE levels and the combined RAST index. RsaI_ex7 was also associated with loge blood eosinophil counts. These associations were independent of age, sex and familial correlations. CONCLUSION: This study supports a role for the FcepsilonR1-beta gene or a nearby gene in the pathogenesis of asthma.
  • Journal article
    Vigushin DM, Ali S, Pace P, Ito K, Adcock I, Coombes RCet al., 1999,

    Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer <i>in vivo</i>.

    , CLINICAL CANCER RESEARCH, Vol: 5, Pages: 3777S-3777S, ISSN: 1078-0432
  • Journal article
    Clarke J, Cota E, Fowler SB, Hamill SJet al., 1999,

    Folding studies of immunoglobulin-like β-sandwich proteins suggest that they share a common folding pathway

    , STRUCTURE WITH FOLDING & DESIGN, Vol: 7, Pages: 1145-1153, ISSN: 0969-2126
  • Journal article
    Negrete-Urtasun S, Reiter W, Diez E, Denison SH, Tilburn J, Espeso EA, Peñalva MA, Arst HNet al., 1999,

    Ambient pH signal transduction in <i>Aspergillus</i>:: completion of gene characterization

    , MOLECULAR MICROBIOLOGY, Vol: 33, Pages: 994-1003, ISSN: 0950-382X

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