Histone ligands

Depletion of histone HI after covalent modification from chromatin is a key step in eukaryotic transcription (Lee et al, 1993 Juan et al, 1994 Rice and Allis, 2001). A comparison of the association of the antibiotic Mg + complexes with the normal and HI depleted chromatin suggests that smaller ligands, like anticancer drugs, have better accessibility for HI depleted chromatin compared to native chromatin. HI depleted chromatin is also more prone to aggregation upon association with the complex I of the antibiotic Mg + complexes. It is also less accessible to micrococcal nuclease. We propose that HI depleted chromatin is a better target of these antibiotics compared to native chromatin. This observation is particularly significant in case of neoplastic cells where most of the cell nuclei are transcriptionally active, and, therefore, contain HI depleted chromatin. 

Role of N-terminal tails of nucleosome core histones to the accessibility of small ligands... 

Monden T, Wondisford FE, Hollenberg AN (1997) Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein. J Biol Chem 272 29834-29841 Moore SD, Herrick SR, Ince TA, Kleinman MS, Cin PD, Morton CC, Quade BJ (2004) Uterine leiomyomata with t(10 17) disrupt the histone acetyltransferase MORF. Cancer Res 64 5570-5577... 

Thyroid Hormone Receptor (TR) can bind to the LTR in vivo independently of its ligand and regulates promoter activity. ChIP assays with anti-acetylated-histone antibodies revealed that unliganded TR reduce the local histone acetylation levels at the HIV-1 LTR, while thyroid hormone treatment reverses this induction (Hsia and Shi, 2002). Accordingly, unliganded TR recruits co repressors and at least one HDAC (Hsia and Shi, 2002). 

Click RD, Swendeman SL, Coffey DC, Rifkind RA, Marks PA, Richon VM, La Quaglia MR (1999) Hybrid polar histone deacetylase inhibitor induces apoptosis and CD95/CD95 ligand expression in human neuroblastoma. 

Kwon SH, Ahn SH, Kim YK, Bae GU, Yoon JW, Hong S, Lee HY, Lee YW, Lee HW, Han JW. (2002) Apicidin, a histone deacetylase inhibitor, induces apoptosis and Fas/Fas ligand expression in human acute promyelocytic leukemia cells. J Biol Chem 111 2073-2080. 

Bhuiyan MPI, Kato T, Okauchi T, Nishino N, Mueda S, Nishino TG, Yoshida M. (2006) Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases. Bioorg Med Chem Lett 14 3438-3446. 

Mazitschek, R., Patel, V., Wirth, D.F. and Clardy, J. (2008) Development of a fluorescence polarization based assay for histone deacetylase ligand discovery. Bioorganic Medicinal Chemistry Letters, 18, 2809-2812. 

Mai, A., Cheng, D., Bedford, M.T, Valente, S., Nebbioso, A., Perrone, A., Brosch, G., Sbardella, G., De Beilis, F., Miceli, M. and Altucci, L. (2008) Epigenetic multiple ligands Mixed histone/protein methyltransferase, acetyltransferase, and class 111 deacetylase (sirtuin) inhibitors. Journal of Medicinal Chemistry, 51, 2279-2290. 

Glass, C.K., Eu, X.D. and Roserrfeld, M.G. (2007) Histone mefhylation-dependent mechanisms impose ligand dependency for gene activation by nudear receptors. Cell, 128, 505-518. 

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]. 

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