Histone deacetylase activity

The antagonist-induced conformation of nuclear hormone receptors attracts co-repressors like Nco/SMRT (nuclear hormone receptor co-repressor/silencing mediator of retinoid and thyroid receptors) which further recruit other nuclear proteins with histone deacetylase activity. Their action leads to chromatin condensation, thus preventing the general transcription apparatus from binding to promoter regions. 

Boutillier AL, Trinh E, Loeffler JP (2003) Selective E2E-dependent gene transcription is controlled by histone deacetylase activity during neuronal apoptosis. J Neurochem 84(4) 814-828 Buck SW, Gallo CM, Smith JS (2004) Diversity in the Sir2 family of protein deacetylases. J Leukoc Biol 75(6) 939-950... 

Davie JR (2003) Inhibition of histone deacetylase activity by butyrate. J Nutr 133(7 Suppl) 2485S-2493S Detich N, Bovenzi V, Szyf M (2003) Valproate induces replication-independent active DNA demethy-lation. J Biol Chem 278(30) 27586-27592... 

Xue, Y., Wong, J., Moreno, G.T., Young, M.K., Cote, J., and Wang, W. (1998) NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol. Cell 2, 851-861. 

Davie JR. (2003) Inhibition of histone deacetylase activity by butyrate. JNutr 133 2485S-2493S. 

Nian H, Delage B, Ho E, Dashwood RH. (2009) Modulation of histone deacetylase activity by dietary isothio-cyanates and allyl sulfides Studies with sulforaphane and garlic organosulfur compounds. Environ Mol Mutagen 50 213-221. 

Ito K, Ito M, Elliott MW, Cosio B, Carmaori G, Kon OM, Barczyk A, Hayashi S, Adcock LM, Hogg JC, Barnes PJ. (2005) Decreased histone deacetylase activity in chronic obstructive pulmonary disease. New Engl J Med 352 1957-1976. 

Hoffmann, K., Brosch, G., Loidl, P. and Jung, M. (1999) A non-isotopic assay for histone deacetylase activity. Nucleic Acids Research, 27, 2057-2058. 

Heltweg, B. and Jung, M. (2002) A microplate reader-based nonisotopic histone deacetylase activity assay. Analytical Biochemistry, 302, 175-183. 

Heltweg, B., Trapp, J. and Jung, M. (2005) In vitro assays for the determination of histone deacetylase activity. Methods (San Diego, Calif), 36, 332-337. 

The first functional cell-based assay for the determination of pan-histone deacetylase activity was achieved by detecting hyperacetylated histones by Western blotting. The histone acetylation level in cells offers a measure of candidate HDACI activity and has been linked to antiproliferative and cytotoxic effects. Beckers et al. used a cellular histone hyperacetylation assay for quantification of the cellular efficacy of HDACIs using the Cellomics Array Scan II platform in 96 wells [14]. The program... 

Pan = Total histone deacetylase activities HD( > = Individual histone deacetylase isoform activity Numbers 36 and 37 correspond to citation references which report pertinent HDAC isoform activity inhibition of compounds (Cpd) ac-H3 and Ac-H4 represent acetylated histone H3 or H4. 

In the absence of ligand, some nuclear hormone receptors associate with co-repressors, namely, SMRT (silencing mediator of retinoic acid and thyroid hormone receptors) and N-CoR (nuclear receptor co-repressor). Both, SMRT and N-CoR, recruit coregulatory protein SINS and histone deacetylases (HDACs) to form a large co-repressor complex that contains histone deacetylase activity, implicating histone deacetylation in transcriptional repression [52,53]. 

Among the general cofactors are also included proteins with histone acetylase activity (HAT) or histone deacetylase activity (HDAC). The acetylation/deacetylation of histones plays a significant role in transcription regulation of chromatin-coated DNA. 

In the case of the T3R and RAR specific repressor proteins have been identified which bind to the receptor and mediate an inhibition of transcription (Hoerlein et al, 1995). The repressor proteins are also termed co-repressors Among the repressors are found proteins with histone deacetylase activity (see 1.4.6). The RXR heterodimers possibly stabilize the repressed state of chromatin by recruiting a histone deacetylase to the chromatin. 

Ito et al A molecular mechanism of action of theophylline Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA 2002 99 8921. [PMID 12070353]... 

Fuks F, Burgers WA, Brehm A, Hughes-Davies L, Kouzarides T. DNA methyltransferase Dnmtl associates with histone deacetylase activity. Nat Genet 2000 24 88-91. 

Ramirez T, Brocher J, Stopper H, Hock R (2008) Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in hitman cells. Chromosoma 117(2) 147-157... 

They succeeded in isolating two nuclear proteins (55 and 50kDa) that co-purified with histone deacetylase activity by using trapoxin affinity matrix, which was created by cross-linking K-trap with Affi-GellO (5). Both proteins... 

Transition of active to inactive states of chromatin (and vice versa) is controlled by epigentic modifications including acteylation of N-terminal Lys residues of histones H3 and H4, methylation of Lys9 of H3 and methylation of CpC sequences. CpC methylation induces binding of Methy-C-binding proteins (MeCP and MDB proteins) which in turn leads to recruitment of histone deacetylase activity (HDAC) establishing a repressed state of the chromatin. 

Methylation of DNA at CpG sequences. Methylated CpG elements are recognized by methyl-CpG binding proteins that recruit histone deacetylase activity and thereby induce an inhibitory chromatin configuration. 

Fig. 4.11 Model of repression and activation of T3R. In the absence of the T3 hormone, a hetero-dimeric RXR-T3R receptor is bound at the T3-re-sponsive element,TRE, establishing a basal repressed state. The repressed state is maintained by recruitment of corepressor complexes containing histone deacetylase activity. X refers to potential unidentified cofactors (possibly chromatin remodeling complexes or SRBs) which help to keep the promotor-bound basal transcription apparatus in...

The mode of action of Smad 4 clearly differs from that of the other members of the Smad family. Smad 4 binds to phosphorylated R-Smads and forms trimeric complexes composed of two R-Smad molecules and one Smad 4 molecule. These complexes translocate to the nucleus, where they bind to related DNA elements and activate the transcription of target genes. The mechanism of transcription regulation by Smads is complex and includes both positive and negative influences. Generally, Smad-dependent regulation of transcription requires the interaction with other transcription factors, such as members of the FoxH 1 family of forkhead transcription factors, the Vitamin D receptor and the c-Jun transcription factor, among others (review Attisano et al., 2001). Futhermore, Smads can interact with coactivators and corepressors of transcription and thereby recruit, e. g., histone acetylase activity or histone deacetylase activity to chromatin. 

Yang PM et al (2010) Inhibition of histone deacetylase activity is a novel function of the antifolate drug methotrexate. Biochem Biophys Res Commun 391(3) 1396-1399... 

A. Liu, P. Casaccia-Bonnefil, Histone deacetylase activity is necessary for oligodendrocyte lineage progression,... 

Billin, S.L. Schreiber, D.E. Ayer, Histone deacetylase activity is required for full transcriptional repression by mSin3A, Cell 1997, 89, 341-347. 

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