Lymphocytes Histones

Yet another example of combinatorial histone codes come to fore in yeast, wherein H2B K123 monoubiquitination was shown to be a necessary prerequisite for H3K24 and H3K79 methylation resulting in opening of the chromatin (Sun and Allis, 2002). Combination of histone marks in the regulation of physiologically relevant processes such as embryonic development and lymphocyte maturation have also been described. 

Messenger RNAs for H2A.Bbd have been detected in human testis, fibroblasts and lymphocytes [77], but little is known about the amount of H2A.Bbd protein in these or other human cell types or about its presence in other species. The distribution of H2A.Bbd in chromatin was examined by expressing epitope-tagged or GFP-tagged H2A.Bbd in cultured cells. These studies revealed a striking deficiency of H2A.Bbd in the inactive X chromosome, leading to its name which stands for Histone H2A Barr-body deficient [77]. The distribution of H2A.Bbd overlapped extensively with that of H4 acetylated on lysine 12, suggesting that H2A.Bbd may preferentially associate with transcriptionally active chromatin. 

Zhang, L., Freitas, MA., Wickham, J., Parthun, M.R., Klisovic, M.I., Marcucd, G. and Byrd, J.C. (2004) Differential expression of histone post-translational modifications in acute myeloid and chronic lymphocytic leukemia determined by high-pressure liquid chromatography and mass spectrometry. Journal of the American Society for Mass Spectrometry, 15, 77-86. 

Millard, C., Meier, H., Broomfield, C. (1994). Exposure of human lymphocytes to bis-(2-chloroethyl)sulfide solubilizes truncated and intact core histones. Biochim. Biophys. Acta 1224 389-94. 

A previously healthy 63-year-old man, who had taken quinidine gluconate 972 mg/day for 9 months, developed diffuse edematous erythema on the extensive surfaces of the hands, arms, and face, with marked accentuation over the joints. His nail-fold capillaries were dilated and the shoulder abductors were shghtly weak. His erythrocyte sedimentation rate was shghtly raised (29 mm/hour) and there was a positive ANA titer (1 640) with a speckled pattern. There were no antibodies to Sm, ribonucleoprotein, SSA or SSB antigens, or histones. There was no evidence of inflammatory myopathy on electromyography, and a skin biopsy showed a mild, superficial, perivascular, lymphocytic inflammation with positive direct immunofluorescence for IgG and IgM at the dermoepidermal junction. There was no evidence of malignancy. All these abnormalities resolved rapidly after quinidine withdrawal. 

One of the most widespread examples of phenylethanoid glycosides is verbascoside, also called acteoside, which has been obtained form sources belonging to different plant families. This compound, isolated from Lantana camara (Verbenaceae), was characterised as an inhibitor of rat brain PKC, with an IC50 value of 25 iM. This effect was abolished by adding ATP, which indicated a competitive interaction with the nucleotide. The inhibition was non-competitive with respect to the phosphate acceptor, histones type IIIS in this case, but other kinases, such as PTK from a lymphoma cell line or PKA, were not inhibited. In order to translate the biochemical effect to a related cellular event, the ability of verbascoside to reduce the proliferation of the lymphocytic mouse leukaemia L-1210 cells was examined. This compound showed an IC50 value of 13 pM [32]. 

In HeLa ceils hydroxyurea is an efficient inhibitor of histone synthesis. This action requires protein synthesis and leads to rapid disappearance of cytoplasmatic histone mRNA The effect is not specific for hydroxyurea since suppression of DNA synthesis by arabino-cytosine or temperature-sensitive mutations yields analogous results. Similarly, the synthesis of some enzymes necessary for DNA replication and active in S-phase is altered by hydroxyurea. Increased activity of ribonucleotide reductase in HeLa and in hamster cells and of the salvage enzyme thymidine kinase in HeLa cells and KB cells has been observed, probably as a consequence of the increased fraction of cells in S-phase. Repression occurs for thymidine kinase in human lymphocytes and for ornithine decarboxylase in Chinese hamster fibroblasts whereas no or only slight effects were seen on ribonucleotide reductase in hamster fibroblasts , on thymidylate synthase in extracts from synchronous mouse cells " , and on DNA polymerase in rabbit kidney cells or HeLa cells . ... 

The lymphocyte transformation test has been extensively used for the detection of lymphocytes specifically allergized to drugs (Halpern et al. 1967 Rocklin and David 1971 Warrington et al. 1979). The assay, however, was found to be unsuitable for the demonstration of hypersensitivity to chloramphenicol (Dobozy et al. 1971). The reason for this lack of reactivity was attributed to the inhibition of protein synthesis by the antibiotic. Using " C-labeled histones, Dobozy et al. (1971) found that chloramphenicol had little influence on the methylation of histones and that enhanced histone methylation could be observed in the cultures of lymphocytes obtained from chloramphenicol allergic patients compared with normal controls. The overall correlation was 100% and the test was recommended as being very useful. 

Dewdney JM (1977) Immunology of the antibiotics. In Sela M (ed) The antigens IV. Academic Press, New York San Francisco London, pp 73-245 Dobozy A, Hunyadi J, Simon H (1971) Demonstration of chloramphenicol hypersensitivity by measurement of histone methylation in lymphocyte cultures. Clin Exp Immunol 8 917-925... 

Watson, K. Edwards, R. J. Shaimak, S. Parmelee, D. C. Sarraf, C. Gooderham, N. J. Davies, D. S. Extra-nuclear location of histones in activated human peripheral-hlood lymphocytes and cultured T-ceUs. Biochem. Pharmacol, 1995, 50(3), 299 309. 

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