Hyperacetylation

Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H (2002) Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35 243-254 Smith MM (2002) Centromeres and variant histones what, where, when and why Curr Opin Cell Biol 14 279-285... 

Taken together, these results show that while hypoacetylation is a feature of neuronal apoptosis, hyperacetylation can also induce death, through common mechanisms. 

As largely detailed in this review, neuroprotection depends on a balance between the enzymes HATS and HDACs and pushing the balance towards hyperacetylation in healthy cells will lead to cell death. For example, at 100 nM, TSA displays... 

Stedman W, Deng Z, Lu F, Lieberman PM (2004) ORC, MCM, and histone hyperacetylation at the Kaposi s sarcoma-associated herpesvirus latent replication origin. J Virol 78 12566-12575 Steiner H, Haass C (2001) Nuclear signaling a common function of presenilin substrates J Mol Neurosci 17 193-198... 

Van Lint C, Emiliani S, Ott M, Verdin E (1996a) Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J 15 1112-1120 Van Lint C, Emiliani S, Verdin E (1996b) The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene Expr 5 245-53 Van Lint C, Amelia CA, Emiliani S, John M, Jie T, Verdin E (1997) Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for vims infectivity. J Virol 71 6113-6127... 

Histones of Plasmodium falciparum represent a new target for antimalarials. Apicidin [Cyclo (N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2-amino-oxodecanoyl] is a potent, broad spectrum antiprotozoal agent. The target of apicidin is Histone deacetylases HDA (Darkin Rattray et al., 1996), evidenced as hyperacetylation of histones in treated parasites. 

Blander G, Guarente L (2004) The Sir2 family of protein deacetylases. Annu Rev of Biochem 73 417 35 Brinkmann H, Dahler AL, Popa C, Serewko MM, Parsons PG, Gabrielli BG, Burgess AJ, Saunders NA (2001) Histone hyperacetylation induced by histone deacetylase inhibitors is not sufficient to cause growth inhibition in human dermal fibroblasts. J Biol Chem 276 22491-22499... 

Recent studies on asthma and CORD have shown variations in the acetylation levels of inflammatory proteins and histones that are altered compared to those without the diseases. In asthma, HAT activity is increased, while HDAC activity remains the same, while those with COPD show the opposite. These studies implicate protein hyperacetylation in inflammatory response and hypoacetylation in the lack of inflammatory response. 

But what should happen upon histone hyperacetylation if nucleosomes, on average, do not overtwist DNA Then no change in (ALkn) should be observed. 

Fig. 11. Effects of histone acetylation on the folding and stability of the nucleosome core particle. A. NaCl dependence of the sedimentation coefficient (s2o,w) of the nucleosome core particles with different extent of acetylation soo D] [379]. B. Dose-response curves obtained with hypo- ( ) and hyperacetylated...

A. Effect of the ionic strength (mM NaCl concentration) on the average sedimentation coelRcient (S20,w) of (208-12) oligonucleosome arrays reconstituted with HeLa cell native histone octamers [solid line, ], chicken erythrocyte histone octamers (broken line) [369], or hyperacetylated. HeLa cell histones 208-12 oligonucleosome complexes reconstituted with hyperacetylated HeLa cell histones ( ) [369]. 

B. Effect of the ionic strength on hyperacetylated 208-12 nucleosome arrays as visualized by electron microscopy. The numbers to the left indicate the milimolar NaCl concentration [369]. [Reproduced from Garcia-Ramirez M. et al. (1995) J. Biol. Chem. 270, 17923-17928, with permission from The American Society for Biochemistry and Molecular Biology.]... 

Finally, targeted active demethylation has been put forward as an explanation for the unmethylated state of CpG islands (Fig. 3e). In this model, features of active chromatin structure (e.g., histone hyperacetylation) cause active demethylation of associated sequences [43,44]. Based on a broad analysis of existing data, Szyf... 

Oliva, R., Bazett-Jones, D.P., Locklear, L., and Dixon, G.H. (1990) Histone hyperacetylation can induce unfolding of the nucleosome core particle. Nucleic Acids Res. 18(9), 2739-2747. 

Subsaturated reconstituted nucleosomal arrays from 208-12 DNA fragment and HeLa control or hyperacetylated core histones... 

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