Histone pathways

Despite the complexity of the experiments and the enormous data manipulation necessary, complex biological pathways, as well as new drug targets are being identified by this method. Examples include screens for compounds that arrest cells in mitosis, that block cell migration, and that block the secretory pathway [50], or assays with primary T cells from PLP TCR transgenic mice for their inhibitory activity on the proliferation and secretion of proinflammatory cytokines in PLP-reactive T cells [51], and identification of small-molecule inhibitors of histone acetyltransferase activity [52]. 

Tagami H, Ray-Gallet D, Almouzni G, Nakatani Y (2004) Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 116 51-61 Taneja N, Davis M, Choy JS, Beckett MA, Singh R, Kron SJ, Weichselbaum RR (2004) Histone H2AX phosphorylation as a predictor of radiosensitivity and target for radiotherapy. J Biol Chem 279 2273-2280... 

Ueda K, Kinoshita Y, Xu ZJ, Ide N, Ono M, Akahori Y, Tanaka I, Inoue M (2000) Unusual core histones specifically expressed in male gametic cells of Lilium longiflorum. Chromosoma 108 491—500 Unal E, Arbel-Eden A, Sattler U, Shroff R, Lichten M, Haber JE, Koshland D (2004) DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol Cell 16 991-1002... 

Figure 1. Different histone chaperones in the key histone metabolic pathways Functions of histone chaperones range from the storage of newly synthesized histones in the cytoplasm, its transfer into the nucleus and in histone assembly into nucleosomes. Apart from diis die histone chaperones are also involved in histone exchange, maintenance of heterochromatin and in the regulation of chromatin structure during transcription. (See Colour Plate 10.)...

Munakata T, Adachi N, Yokoyama N, Kuzuhara T, Horikoshi M (2000) A human homolog of yeast anti-silencing factor has histone chaperone activity. Genes to Cells 5 221-233 Okuwaki M, Matsumoto K, Tsujimoto M, Nagata K (2001) Function of nucleophosmin/B23, a nuclear acidic protein, as a histone chaperone. FEBS Lett 506 272-276 Owen-Hughes T (2003) Colworth memorial lecture. Pathways for remodeling chromatin. Biochem. Soc.Trans 31 893-905... 

Polo SE, Almouzni G (2005). Histone metabolic pathways and chromatin assembly factors as proliferation markers Cancer Lett 220 1-9... 

Legube G, Linares LK, Tyteca S, Caron C, Scheffner M, Chevillard-Briet M, Trouche D (2004) Role of the histone acetyl transferase Tip60 in the p53 pathway. J Biol Chem 279 44825 4833 Linggi BE, Brandt SJ, Sun ZW, Hiebert SW (2005) Translating the histone code into leukemia. J Cell Biochem 96 938-950... 

Schmitt A, Gutierrez GJ, Lenart P, Ellenberg J, Nebreda AR (2002) Histone H3 phosphorylation during Xenopus oocyte maturation regulation by the MAP kinase/p90Rsk pathway and uncoupling from DNA condensation. EEBS Lett 518(l-3) 23-28... 

Mosammaparast N, Guo Y, Shabanowitz J, Hunt DF, Pemberton LF (2002) Pathways mediating the nuclear import of histones H3 and H4 in yeast. J Biol Chem 277 862—868 Mosammaparast N, Jackson KR, Guo Y, Brame CJ, Shabanowitz J, Hunt DF, Pemberton LF (2001) Nuclear import of histone H2A and H2B is mediated by a network of karyopherins. J Cell Biol... 

The absence of a transactivation-competent NF-kB heterodimer in the nucleus of latently infected resting memory CD4+ T cells could contribute to latency. Activation of the NF-kB pathway leading to migration of a transactivating heterodimer such as p50/p65 could allow viral reactivation. In the absence of induction, NF-kB p50-HDACl complexes constitutively bind the latent HIV-1 LTR (Williams et al, 2006). NF-kB p50 does not possess a transactivation domain. These p50-HDACl complexes induce histone deacetylation and repressive changes in chromatin structure of the HIV-1 LTR (Williams et al, 2006). Knockdown of p50 expression reduces HDACl binding to the latent HIV-1 LTR and induces RNA polymerase II recruitment (Williams et al, 2006). Concomitantly with HIV-1 transcriptional activation, the p65 subunit and different HATs are recruited to the viral promoter (Lusic et al, 2003 Thierry et al, 2004). 

Skov S, Rieneck K, Bovin LE, Skak K, Toim-a S, Michelsen BK, Odum N (2003) Histone deacetylase inhibitors a new class of iimnimosuppressors targeting a novel signal pathway essential for CD154 expression. Blood 101 1430-1438... 

The results obtained from the histone acetylation and phosphorylation studies suggest that cyclo(Trp-Trp) and cyclo(Pro-Trp) induce differential gene expression through different signal transduction pathways. Cyclo(Trp-Trp) induced the highest level of acetylation of histones whereas cyclo(Phe-Pro) induced high levels of phosphorylation of histones." ... 

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