By Mouldy, Ed. Sioud
Read or Download Target Discovery and Validation Reviews and Protocols, Vol 2: Emerging Molecular Targets and Treatment Options (Methods in Molecular Biology Vol 361) PDF
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Additional info for Target Discovery and Validation Reviews and Protocols, Vol 2: Emerging Molecular Targets and Treatment Options (Methods in Molecular Biology Vol 361)
Sample text
DNA Methylation and Histone Modifications 43 Reactivating genes with DNA demethylating agents is an encouraging discovery with respect to avoiding toxic effects. However, it is important to note that the hypermethylation of CpG islands occurs in conjunction with the action of methyl-binding proteins, histone hypoacetylation, and histone methylation, which all contribute to formation of a closed chromatin state and transcriptional silencing (83). Several clinical trials to study these and other mechanisms in patients with cancer are underway in United States and Europe.
R. , and Schwartsmann, G. (2002) Targeting protein kinase C: new terapeutic opportunities against high-grade malignant gliomas. The Oncologist 7, 17–33. 66. Sioud, M. and Sørensen, D. R. (1998) A nuclease-resistant protein kinase C alpha ribozyme blocks glioma cell growth. Nat. Biotechnol. 16, 556–561. 67. Leirdal, M. and Sioud, M. (1999) Ribozyme inhinition of the protein kinase Ca triggers apoptosis in glioma cells. Br. J. Cancer. 80, 1558–1564. 24 Sioud and Leirdal 68. Sioud, M. and Leirdal, M.
Note that the nucleosome containing the two turns of DNA has the N-terminal tails of the eight-histone protein sticking out from the nucleosome like the legs of a spider. The structure of the portion of these N-terminal tails outside of the DNA is not known, and, more importantly, nor is the 30-nm chromatin fiber. Tetramerization occurs via interactions between the C-terminal halves of two histone molecules and results in a twofold axis of symmetry for the tetramer as shown. (B) Histone N-terminal tails are exposed from the nucleosomal interior into the aqueous surroundings.