Transcription Factors Belonging (transcription + factor_belonging)

Distribution by Scientific Domains


Selected Abstracts


Immunocytochemical analysis of the circadian clock protein in mouse hepatocytes

MICROSCOPY RESEARCH AND TECHNIQUE, Issue 5 2003
Manuela Malatesta
Abstract Many biochemical, physiological, and behavioral processes in organisms ranging from prokaryotes to humans exhibit circadian rhythms, defined as cyclic oscillations of about 24 hours. The mechanism of the cellular circadian clock relies on interlocking positive and negative transcriptional/translational feedback loops based on the regulated expression of several genes. Clock is one of these genes and its transcript, CLOCK protein, is a transcription factor belonging to the bHLH-PAS family. In mammals the clock gene is expressed in several tissues, including the liver. In the present study, we analyzed by means of quali-quantitative immunoelectron microscopy the fine intracellular distribution of the CLOCK protein in mouse hepatocytes during the daily cycle. We demonstrated that CLOCK protein is mostly located in the cell nucleus, where it accumulates on perichromatin fibrils, representing the in situ form of nascent pre-mRNA, while condensed chromatin and nucleoli contain lower amounts of protein. Moreover, we found that CLOCK protein shows circadian oscillations in these nuclear compartments, peaking in late afternoon. At this time the hepatic transcriptional rate reaches the maximal level, thus suggesting an important role of CLOCK protein in the regulation of liver gene expression. Microsc. Res. Tech. 61:414,418, 2003. © 2003 Wiley-Liss, Inc. [source]


Study of PfMyb1 Transcription Factor Regulation Network during Plasmodium falciparum Erythrocytic Cycle

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005
M. GISSOT
During the complex life cycle of Plasmodium falciparum, the regulation of events that occur during the erythrocytic cycle, such as proliferation and differentiation, implies a fine control of transcriptional activities governing the expression profiles of each gene. However, transcriptional regulation and notably its actors, transcription factors and regulation motifs, are poorly described in Plasmodium. In order to decipher the mechanisms implicated in transcriptional regulation, we studied a transcription factor belonging to the trytophan family and showed that the PfMyb1 protein contained in nuclear extracts has a specific DNA binding activity. We took advantage of long pfmyb1 double stranded RNA (dsRNA) to inactivate the cognate messenger and understand the role of PfMyb1 during the erythrocytic cycle. Culture treated with pfmyb1 dsRNA exhibited a 40% growth inhibition and mortality during trophozoite to schizont transition when compared to either untreated control or culture treated with unrelated long dsRNA. We have further demonstrated that pfmyb1 transcript and protein decreased up to 80% in treated trophozoite culture at the time of pfmyb1 expression peak. Thus, we investigated the effect of this partial loss of transcript and protein using a thematic DNA microarray containing PCR products, representative of P. falciparum genes involved in cell cycle and transcriptional regulation. SAM software enabled us to identify several genes over and under-expressed, potentially directly or indirectly regulated by PfMyb1. These alterations of expression were verified by qPCR and Western blotting. We are currently working on the promoters of those genes to decode determinants of gene regulation by Pfmyb1. [source]


Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-,/-, activator properties

DIABETES OBESITY & METABOLISM, Issue 1 2008
Yuhao Li
PPARs are transcription factors belonging to the superfamily of nuclear receptors. PPAR-, is involved in the regulation of fatty acid (FA) uptake and oxidation, inflammation and vascular function, while PPAR-, participates in FA uptake and storage, glucose homeostasis and inflammation. The PPARs are thus major regulators of lipid and glucose metabolism. Synthetic PPAR-, or PPAR-, agonists have been widely used in the treatment of dyslipidaemia, hyperglycaemia and their complications. However, they are associated with an incidence of adverse events. Given the favourable metabolic effects of both PPAR-, and PPAR-, activators, as well as their potential to modulate vascular disease, combined PPAR-,/-, activation has recently emerged as a promising concept, leading to the development of mixed PPAR-,/-, activators. However, some major side effects associated with the synthetic dual activators have been reported. It is unclear whether this is a specific effect of the particular synthetic compounds or a class effect. To date, a medication that may combine the beneficial metabolic effects of PPAR-, and PPAR-, activation with fewer undesirable side effects has not been successfully developed. Pomegranate plant parts are used traditionally for the treatment of various disorders. However, only pomegranate flower has been prescribed in Unani and Ayurvedic medicines for the treatment of diabetes. This review provides a new understanding of the dual PPAR-,/-, activator properties of pomegranate flower in the potential treatment of diabetes and its associated complications. [source]


Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases?

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2006
Julien Becker
Abstract Lung inflammatory diseases, such as acute lung injury (ALI), asthma, chronic obstructive pulmonary disease (COPD) and lung fibrosis, represent a major health problem worldwide. Although glucocorticoids are the most potent anti-inflammatory drug in asthma, they exhibit major side effects and have poor activity in lung inflammatory disorders such as ALI or COPD. Therefore, there is growing need for the development of alternative or new therapies to treat inflammation in the lung. Peroxisome proliferator-activated receptors (PPARs), including the three isotypes PPAR,, PPAR, (or PPAR,) and PPAR,, are transcription factors belonging to the nuclear hormone receptor superfamily. PPARs, and in particular PPAR, and PPAR,, are well known for their critical role in the regulation of energy homeostasis by controlling expression of a variety of genes involved in lipid and carbohydrate metabolism. Synthetic ligands of the two receptor isotypes, the fibrates and the thiazolidinediones, are clinically used to treat dyslipidaemia and type 2 diabetes, respectively. Recently however, PPAR, and PPAR, have been shown to exert a potent anti-inflammatory activity, mainly through their ability to downregulate pro-inflammatory gene expression and inflammatory cell functions. The present article reviews the current knowledge of the role of PPAR, and PPAR, in controlling inflammation, and presents different findings suggesting that PPAR, and PPAR, activators may be helpful in the treatment of lung inflammatory diseases. [source]


Agonists specific for the transcription factor PPARdelta accelerate differentiation of oligodendrocytes

JOURNAL OF NEUROCHEMISTRY, Issue 2002
R. P. Skoff
Peroxisome proliferator activated receptors (PPARs) are transcription factors belonging to the nuclear hormone receptor superfamily that regulate key genes involved in lipid metabolism. PPAR, is ubiquitously expressed at low levels in many tissues and its function has remained elusive. However, we have shown that PPAR, is abundantly expressed in oligodendrocytes (Ols), suggesting this receptor plays a critical role in oligodendrocyte differentiation (Granneman et al. 1998 J. Neurosci. Res51, 563). We first investigated the effects of PPAR agonists on proliferation and differentiation of Ols in tissue culture. Primary glial and enriched Ol cultures were treated with ligands that specifically activate PPAR, and PPAR, (Berger et al. 1999 J. Biol. Chem. 274, 6717). PPAR, but not PPAR, agonists increased the size of OL membrane sheets within 24 h of application. The increase in membrane sheet size was mirrored by increases in MBP and PLP mRNA's. In enriched Ol cultures, the number of Ols was increased 70% with the PPAR, agonist but not the PPAR, agonist (Saluja et al. 2001 Glia33, 191). In vivo injections of PPAR, agonist into P2 and P3 mice show an increase of total macroglia in the ventral and dorsal funiculi of the spinal cord of 20,40% compared to controls. Preliminary observations suggest the Ols in agonist treated cultures are larger and more densely stained than controls. Our results show for the first time that a specific ligand for a transcription factor is capable of activating the program of Ol differentiation. Acknowledgements: Supported by NMSS. [source]