Acetylation is mediated by acetyltransferases and deacetylases, and occurs not only on histones but also on diverse proteins. Although histone acetylation in chromatin structure and transcription has been well studied, the biological roles of non-histone acetylation remain elusive. Histone deacetylase 6 (Hdac6), a member of the histone deacetylase (HDAC) family, is a unique deacetylase that loc...

Depsipeptide (FK228) is a novel histone deacetylase inhibitor currently in clinical trials and the first to demonstrate clinical activity in patients. Responses have been observed in patients with T-cell lymphomas, despite prior treatment with multiple chemotherapeutic agents. To better understand the effects of histone deacetylase inhibitors on T-cell lymphoma, the human T-cell lymphoma cell l...

AIMS Aberrant histone acetylation has been associated with malignancy and histone deacetylase (HDAC) inhibitors are currently being investigated in numerous clinical trials. So far, the malignancy most sensitive to HDAC inhibitors has been cutaneous T-cell lymphoma (CTCL). The reason for this sensitivity is unclear and studies on HDAC expression and histone acetylation in CTCL are lacking. The ...

BACKGROUND The clinical use of chromatin-modulating drugs, such as histone deacetylase inhibitors, for the treatment of bone marrow failure and hematopoietic malignancies has increased dramatically over the last few years. Nonetheless, little is currently known concerning their effects on myelopoiesis. DESIGN AND METHODS We utilized an ex vivo differentiation system in which umbilical cord bl...

Histone deacetylase and chromatin assembly contribute to the control of transcription of the Xenopus TRbetaA gene promoter by the heterodimer of Xenopus thyroid hormone receptor and 9-cis retinoic acid receptor (TR-RXR). Addition of the histone deacetylase inhibitor Trichostatin A (TSA) relieves repression of transcription due to chromatin assembly following microinjection of templates into Xen...

Eight N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes were efficiently prepared as sulfur analogues of Tubastatin A and thus evaluated as new HDAC6 inhibitors. All compounds exhibited potency against HDAC6, and four of them were active in the nanomolar range (IC(50) = 1.9-22 nM). Further analysis revealed that the sulfone derivatives (designated as Tubathians) are superior...

The transcriptional activator CLOCK is a histone acetyltransferase that is required for the circadian expression of many genes. Asher et al. (2008) and Nakahata et al. (2008) now demonstrate that the NAD(+)-dependent enzyme SIRT1 functions as a histone deacetylase that counteracts the activity of CLOCK. These results broaden our understanding of the impact of cellular metabolism on the circadia...