Image cytometric study of pathological specimens or cell lines has suggested that epigenetic mechanisms are likely to play a major role in determining chromatin patterns evaluable through nuclear texture analysis. We previously reported that nuclear textural changes observed in the OV1-VCR etoposide-resistant ovarian carcinoma cell line were associated with an increased acetylated histone H4 le...

Whereas TGF-beta is essential for the development of peripherally induced Foxp3(+) regulatory T cells (iTreg cells) and Th17 cells, the intracellular signaling mechanism by which TGF-beta regulates development of both cell subsets is less understood. In this study, we report that neither Smad2 nor Smad3 gene deficiency abrogates TGF-beta-dependent iTreg induction by a deacetylase inhibitor tric...

Blocking histone deacetylation with trichostatin A (TSA) or blocking cytosine methylation using 5-aza-2'-deoxycytosine (aza-dC) can derepress silenced genes in multicellular eukaryotes, including animals and plants. We questioned whether DNA methylation and histone deacetylation overlap in the regulation of endogenous plant genes by monitoring changes in expression of approximately 7800 Arabido...

We previously identified (Hwang DY and Ismail-Beigi F. Am J Physiol Cell Physiol 281: C1365-C1372, 2001) a 44-bp GC-rich segment of the rat proximal glucose transporter (Glut)1 promoter, located at -104 to -61, as necessary for basal transcription of the Glut1 gene. Using deletion and mutational analysis and expression of transfected reporter constructs, we report in the present study that muta...

Histone deacetylase inhibitors (HDACi) are currently used in the routine clinical treatment of cancer. Alongside the antitumor activity of HDACi, increased attention has been paid to their anti‑inflammatory effects. The present study aimed to analyze the inhibitory effects of the HDACi Trichostatin A (TSA), on the release of inflammatory mediators from macrophages differentiated from U‑937 cell...

The mechanistic basis for the tissue specific expression of cholesterol elimination pathways is poorly understood. To gain additional insight into this phenomenon we considered it of interest to investigate if epigenetic mechanisms are involved in the regulation of the brain-specific enzyme cholesterol 24-hydroxylase (CYP46A1), a key regulator of brain cholesterol elimination. We demonstrated a...

Recently we have demonstrated the possibility to replace histones with protamine, through the heterologous expression of human protamine 1 (hPrm1) gene in sheep fibroblasts. Here we have optimized protaminization of somatic nucleus by adjusting the best concentration and exposure time to trichostatin A (TSA) in serum-starved fibroblasts (nuclear quiescence), before expressing Prm1 gene. To stop...

The histone deacetylase inhibitor trichostatin A (TSA) has been demonstrated to alleviate certain symptoms associated with osteoarthritis (OA). However, the exact mechanisms underlying this protective effect remain to be elucidated. The present study therefore examined the effects of TSA on the expression levels of interleukin‑1β (IL‑1β)-induced matrix metalloproteinases (MMPs) and tissue inhib...

HDAC10 belongs to the class II histone deacetylase family; however, its functions remain enigmatic. We report here that the HDAC10 protein complex contained deacetylated chaperone protein hsc70, and HDAC10 relieved repression of melanogenesis by decreasing the repressional activity of two transcriptional regulators, paired box protein 3 (Pax3) and KRAB-associated protein 1 (KAP1). HDAC10 physic...

In yeast, telomere position effect (TPE) results in the reversible silencing of genes near telomeres. Here we demonstrate the presence of TPE in human cells. HeLa clones containing a luciferase reporter adjacent to a newly formed telomere express 10 times less luciferase than do control clones generated by random integration. Luciferase expression is restored by trichostatin A, a histone deacet...