Search results for "Histone"

Androgen receptor activation by polychlorinated biphenyls

2013

The exposure to environmental endocrine disrupting compounds (EDC), as polychlorinated biphenyls (PCBs), widely diffused in the environment may produce epigenetic changes that affect the endocrine system. We found that PCBs activate AR transcriptional activity and that this effect is potentiated by the demethylase Jarid1b, a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by PCB. The aim of the present study was to investigate the effect of the treatment of cultured cells (HEK293) with a mixture of the most diffused environmental PCBs and, also with dihydrotestosterone (DHT), on the functional interaction between AR and Jarid1b. …

2021

Late-stage colorectal cancer (CRC) is still a clinically challenging problem. The activity of the tumor suppressor p53 is regulated via posttranslational modifications (PTMs). While the relevance of p53 C-terminal acetylation for transcriptional regulation is well-defined, it is unknown whether this PTM controls mitochondrially mediated apoptosis directly. We used wild-type p53 or p53-negative human CRC cells, cells with acetylation-defective p53, transformation assays, CRC organoids, and xenograft mouse models to assess how p53 acetylation determines cellular stress responses. The topoisomerase-1 inhibitor irinotecan induces acetylation of several lysine residues within p53. Inhibition of …

823: 3-deazaneplanocin A (DZNep), an inhibitor of histone methyltransferase EZH2, induces apoptosis and reduces cell migration in chondrosarcoma cells

2014

Histone deacetylase inhibitors: apoptotic effects and clinical implications (Review).

2008

It has been shown that epigenetic modifications play an important role in tumorigenesis. Thus, affecting epigenetic tumorigenic alterations can represent a promising strategy for anticancer targeted therapy. Among the key chromatin modifying enzymes which influence gene expression, histone acetyltransferases (HATs) and histone deacetylases (HDACs) have recently attracted interest because of their impact on tumor development and progression. Increased expression of HDACs and disrupted activities of HATs have been found in several tumor types, with a consequent hypoacetylated state of chromatin that can be strictly correlated with low expression of either tumor suppressor or pro-apoptotic gen…

Epigenetic changes and nuclear factor-κB activation, but not microRNA-224, downregulate Raf-1 kinase inhibitor protein in triple-negative breast canc…

2015

Raf-1 kinase inhibitor protein (RKIP) is a tumor suppressor and metastasis inhibitor, which enhances drug-induced apoptosis of cancer cells. Downregulation of RKIP may be significant in the biology of highly aggressive and drug-resistant tumors, for example triple-negative breast cancers (TNBCs). Potential causes for the low levels of RKIP expressed by SUM 159 TNBC cells were investigated in the present study. Bisulphite modification, methylation specific-polymerase chain reaction (PCR) and a TransAM NF-κB assay were performed and the results suggested that various mechanisms, including methylation of the gene promoter, histone deacetylation and nuclear factor-κB (NF-κB) activation, but not…

Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure

2008

AIMS: Recent studies have demonstrated the importance of chromatin remodelling via histone acetylation/deacetylation for the control of cardiac gene expression. Specific histone deacetylases (HDACs) can, in fact, play a positive or negative role in determining cardiac myocyte (CM) size. Here, we report on the effect on hypertrophy development of three inhibitors (HDACi) of class I HDACs. METHODS AND RESULTS: The compounds were first analysed in vitro by scoring hypertrophy, expression of foetal genes, and apoptosis of neonatal rat CMs stimulated with phenylephrine, an alpha1-adrenergic agonist. This initial screening indicated that a truncated derivative of apicidin with class I HDAC specif…

Emerging functions of nitric oxide in plant immunity

2016

SPEIPMUBAgrosupCNRS; The importance of nitric oxide (NO) in innate and adaptive immunity in mammals is well recognised. NO exerts antimicrobial properties against invaders but also displays immunoregulatory functions in which S-nitrosylation represents a signalling process of major importance. Over the last two decades, a growing body of evidence suggests that NO is also a major component of plant immunity. Our understanding of its role in plant defence has been enriched by the identification and functional analysis of S-nitrosylated proteins. The recent identification of new S-nitrosylated proteins including the chaperone-like enzyme cell division cycle 48 (CDC48), histone deacetylases (HD…

Chromatin Domains and Regulation of Transcription

2007

Compartmentalization and compaction of DNA in the nucleus is the characteristic feature of eukaryotic cells. A fully extended DNA molecule has to be compacted 100,000 times to fit within the nucleus. At the same time it is critical that various DNA regions remain accessible for interaction with regulatory factors and transcription/replication factories. This puzzle is solved at the level of DNA packaging in chromatin that occurs in several steps: rolling of DNA onto nucleosomes, compaction of nucleosome fiber with formation of the so-called 30 nm fiber, and folding of the latter into the giant (50-200 kbp) loops, fixed onto the protein skeleton, the nuclear matrix. The general assumption is…

Subcellular localization and nucleosome specificity of yeast histone acetyltransferases

1991

We have previously reported [López-Rodas et al. (1989) J. Biol. Chem. 264, 19028-19033] that the yeast Saccharomyces cerevisiae contains four histone acetyltransferases, which can be resolved by ion-exchange chromatography, and their specificity toward yeast free histones was studied. In the present contribution we show that three of the enzymes are nuclear, type A histone acetyltransferases and they are able to acetylate nucleosome-bound histones. They differ in their histone specificity. Enzyme A1 acetylates H2A in chicken nucleosomes, although it is specific for yeast free H2B; histone acetyltransferase A2 is highly specific for H3, and histone acetyltransferase A3 preparations acetylate…

Properties of the yeast nuclear histone deacetylase.

1994

A nuclear histone deacetylase from yeast was partially purified and some of its characteristics were studied. Histone deacetylase activity was stimulated in vitro by high-mobility-group nonhistone chromatin proteins 1 and 2 and ubiquitin and inhibited by spermine and spermidine, whereas n-butyrate had no significant inhibitory effect. Like the mammalian enzyme, partially purified histone deacetylase from yeast was strongly inhibited by trichostatin A. However, in crude extract preparations the yeast enzyme was not inhibited and treatment with trichostatin in vivo did not show any effect, either on the histone acetylation level or on cell viability. At low ionic strength, the enzyme can be i…