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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The SWI/SNF family of ATP-dependent chromatin-remodeling factors plays a central role in eukaryotic transcriptional regulation. In yeast and human cells, two subclasses have been recognized: one comprises yeast SWI/SNF and human BAF, and the other includes yeast RSC and human PBAF. Therefore, it was puzzling that Drosophila appeared to contain only a single SWI/SNF-type remodeler, the Brahma (BRM) complex. Here, we report the identification of two novel BRM complex-associated proteins: Drosophila Polybromo and BAP170, a conserved protein not described previously. Biochemical analysis established that Drosophila contains two distinct BRM complexes: (i) the BAP complex, defined by the presence of OSA and the absence of Polybromo and BAP170, and (ii) the PBAP complex, containing Polybromo and BAP170 but lacking OSA. Determination of the genome-wide distributions of OSA and Polybromo on larval salivary gland polytene chromosomes revealed that BAP and PBAP display overlapping but distinct distribution patterns. Both complexes associate predominantly with regions of open, hyperacetylated chromatin but are largely excluded from Polycomb-bound repressive chromatin. We conclude that, like yeast and human cells, Drosophila cells express two distinct subclasses of the SWI/SNF family. Our results support a close reciprocity of chromatin regulation by ATP-dependent remodelers and histone-modifying enzymes.
Mol Cell Biol 2004 Apr
PMID:Differential targeting of two distinct SWI/SNF-related Drosophila chromatin-remodeling complexes. 1506 Jan 32

Accuracy in microarray technology requires new approaches to microarray reader development. A microarray reader system (optical scanning array or OSA reader) based on automated microscopy with large field of view, high speed 3 axis scanning at multiple narrow-band spectra of excitation light has been developed. It allows fast capture of high-resolution, multi-fluorescence images and is characterized by a linear dynamic range and sensitivity comparable to commonly used photo-multiplier tube (PMT)-based laser scanner. Controlled by high performance software, the instrument can be used for scanning and quantitative analysis of any type of dry microarray. Studies implying temperature-controlled hybridization chamber containing a microarray can also be performed. This enables the registration of kinetics and melting curves. This feature is required in a wide range of on-chip chemical and enzymatic reactions including on-chip PCR amplification. We used the OSA reader for the characterization of hybridization and melting behaviour of oligonucleotide:oligonucleotide duplexes on three-dimensional Code Link slides.
Cell Mol Biol (Noisy-le-grand) 2004 May
PMID:Innovative instrumentation for microarray scanning and analysis: application for characterization of oligonucleotide duplexes behavior. 1520 42

Drosophila BAP and PBAP represent two evolutionarily conserved subclasses of SWI/SNF chromatin remodelers. The two complexes share the same core subunits, including the BRM ATPase, but differ in a few signature subunits: OSA defines BAP, whereas Polybromo (PB) and BAP170 specify PBAP. Here, we present a comprehensive structure-function analysis of BAP and PBAP. An RNA interference knockdown survey revealed that the core subunits BRM and MOR are critical for the structural integrity of both complexes. Whole-genome expression profiling suggested that the SWI/SNF core complex is largely dysfunctional in cells. Regulation of the majority of target genes required the signature subunit OSA, PB, or BAP170, suggesting that SWI/SNF remodelers function mostly as holoenzymes. BAP and PBAP execute similar, independent, or antagonistic functions in transcription control and appear to direct mostly distinct biological processes. BAP, but not PBAP, is required for cell cycle progression through mitosis. Because in yeast the PBAP-homologous complex, RSC, controls cell cycle progression, our finding reveals a functional switch during evolution. BAP mediates G(2)/M transition through direct regulation of string/cdc25. Its signature subunit, OSA, is required for directing BAP to the string/cdc25 promoter. Our results suggest that the core subunits play architectural and enzymatic roles but that the signature subunits determine most of the functional specificity of SWI/SNF holoenzymes in general gene control.
Mol Cell Biol 2007 Jan
PMID:Functional differentiation of SWI/SNF remodelers in transcription and cell cycle control. 1710 3

Although obstructive sleep apnea (OSA) is an independent risk factor for hypertension, the underlying mechanisms are not clearly understood. Apnea and hypopnea episodes during sleep lead to sympathoactivation, decrease plasma pH, and predispose to sodium and volume retention. We hypothesized that, the latter could stimulate digitalis-like natriuretic/vasopressor hormones, endogenous ouabain (EO) and marinobufagenin (MBG). Overnight polysomnography (Embletta) and 24 hrs blood pressure monitoring (SpaceLab 90207) was conducted in 52 consecutive patients with OSA (51 +/- 8 years; 40 males, 12 females) and in 48 age-matched hypertensive subjects without OSA. According to the polysomnography data, 17 patients had a mild degree of OSA (apnea/hypopnea index (AHI) 5-15), 17 patients-moderate (AHI 15-30) and 18 -severe OSA (AHI >30). Levels of MBG excretion co-varied with OSA severity (0.5 +/- 0.1, 0.9 +/- 0.04 and 1.2 +/- 0.06 nmoles per 24 hrs, respectively), while excretion of EO did not differ in patients with different degrees of OSA severity. Our observations suggest that MBG may be involved in the pathogenesis of hypertension in OSA, and may be a marker of OSA severity.
Cell Mol Biol (Noisy-le-grand) 2006 Dec 30
PMID:Marinobufagenin in hypertensive patients with obstructive sleep apnea. 1753 32

Obstructive sleep apnea (OSA) syndrome is a respiratory disease that is linked to heart attacks and high blood pressure. In the present study, we used the Comet assay to compare basal DNA damage and DNA damage induction by hydrogen peroxide, ethanol, and gamma-irradiation in lymphocytes from 35 OSA patients and 35 controls. We also measured the apoptosis and necrosis produced by these agents and the ability of the lymphocytes to repair the induced DNA damage. It was found that lymphocytes isolated from OSA patients had higher basal levels of DNA damage and were more sensitive to the effects of the DNA-damaging agents than lymphocytes from controls. OSA patients also had a reduced capacity to repair the DNA damage induced by the three agents, but apoptosis and necrosis were similar in OSA patients and the controls.
Environ Mol Mutagen 2007 Dec
PMID:DNA damage and repair capacity in lymphocytes from obstructive sleep apnea patients. 1797 9

SWI/SNF ATP-dependent chromatin remodeling complexes (remodelers) perform critical functions in eukaryotic gene expression control. BAP and PBAP are the fly representatives of the two evolutionarily conserved major subclasses of SWI/SNF remodelers. Both complexes share seven core subunits, including the Brahma ATPase, but differ in a few signature subunits; POLYBROMO and BAP170 specify PBAP, whereas OSA defines BAP. Here, we show that the transcriptional coactivator and PHD finger protein SAYP is a novel PBAP subunit. Biochemical analysis established that SAYP is tightly associated with PBAP but absent from BAP. SAYP, POLYBROMO, and BAP170 display an intimately overlapping distribution on larval salivary gland polytene chromosomes. Genome-wide expression analysis revealed that SAYP is critical for PBAP-dependent transcription. SAYP is required for normal development and interacts genetically with core- and PBAP-selective subunits. Genetic analysis suggested that, like BAP, PBAP also counteracts Polycomb silencing. SAYP appears to be a key architectural component required for the integrity and association of the PBAP-specific module. We conclude that SAYP is a signature subunit that plays a major role in the functional specificity of the PBAP holoenzyme.
Mol Cell Biol 2008 May
PMID:The transcriptional coactivator SAYP is a trithorax group signature subunit of the PBAP chromatin remodeling complex. 1829 90

Obstructive sleep apnea, characterized by intermittent periods of hypoxemia, is an independent risk factor for the development of pulmonary hypertension. However, the exact mechanisms of this disorder remain to be defined. Enhanced NADPH oxidase expression and superoxide (O2(-).) generation in the pulmonary vasculature play a critical role in hypoxia-induced pulmonary hypertension. Therefore, the current study explores the hypothesis that chronic intermittent hypoxia (CIH) causes pulmonary hypertension, in part, by increasing NADPH oxidase-derived reactive oxygen species (ROS) that contribute to pulmonary vascular remodeling and hypertension. To test this hypothesis, male C57Bl/6 mice and gp91phox knockout mice were exposed to CIH for 8 hours per day, 5 days per week for 8 weeks. CIH mice were placed in a chamber where the oxygen concentration was cycled between 21% and 10% O2 45 times per hour. Exposure to CIH for 8 weeks increased right ventricular systolic pressure (RVSP), right ventricle (RV):left ventricle (LV) + septum (S) weight ratio, an index of RV hypertrophy, and thickness of the right ventricular anterior wall as measured by echocardiography. CIH exposure also caused pulmonary vascular remodeling as demonstrated by increased muscularization of the distal pulmonary vasculature. CIH-induced pulmonary hypertension was associated with increased lung levels of the NADPH oxidase subunits, Nox4 and p22phox, as well as increased activity of platelet-derived growth factor receptor beta and its associated downstream effector, Akt kinase. These CIH-induced derangements were attenuated in similarly treated gp91phox knockout mice. These findings demonstrate that NADPH oxidase-derived ROS contribute to the development of pulmonary vascular remodeling and hypertension caused by CIH.
Am J Respir Cell Mol Biol 2009 May
PMID:The role of NADPH oxidase in chronic intermittent hypoxia-induced pulmonary hypertension in mice. 1895 68

Many fundamental questions about sleep remain unanswered. The presence of sleep across phyla suggests that it must serve a basic cellular and/or molecular function. Microarray studies, performed in several model systems, have identified classes of genes that are sleep-state regulated. This has led to the following concepts: first, a function of sleep is to maintain synaptic homeostasis; second, sleep is a stage of macromolecule biosynthesis; third, extending wakefulness leads to downregulation of several important metabolic pathways; and, fourth, extending wakefulness leads to endoplasmic reticulum stress. In human studies, microarrays are being applied to the identification of biomarkers for sleepiness and for the common debilitating condition of obstructive sleep apnea.
Trends Mol Med 2009 Feb
PMID:What are microarrays teaching us about sleep? 1916 50

Obstructive Sleep Apnea (OSA) is a prevalent disease that has emerged as a new cerebrovascular disease (CVD) risk factor, which is independent of its association to hypertension, age and other known conditions that increase CVD. The mechanisms involved in this relation are most likely induced by the periodic hypoxia/reoxygenation that characteristically occurs in OSA, which results in oxidative stress, endothelial dysfunction and activation of the inflammatory cascade, all of which favor atherogenesis. Numerous markers of these changes have been reported in OSA patients, including increased circulating free radicals, increased lipid peroxidation, decreased antioxidant capacity, elevation of tumor necrosis factor and interleukines, increased levels of proinflammatory nuclear transcription factor kappa B, decreased circulating nitric oxide, elevation of vascular adhesion molecules and vascular endothelial growth factor. In addition, several authors have described that Continuous Positive Airway Pressure, the standard OSA therapy, reverts these abnormalities. Further research is needed in order to better clarify the complex mechanisms that underlie the relation between OSA, atherogenesis and CVD which most likely will have significant clinical impact.
Curr Mol Med 2009 Mar
PMID:Obstructive sleep apnea as an independent stroke risk factor: possible mechanisms. 1927 28

Obesity and inflammation are known to correlate with the pathogenesis of obstructive sleep apnea syndrome (OSAS). Interleukin (IL)-6, an important regulator of obesity and inflammation, was reported to phenotypically increase in patients with OSAS. This study aimed to investigate whether genetic variants in IL-6 confer susceptibility to OSAS. The study population consisted of 151 patients with OSAS and 75 healthy controls from Southeast China. Five haplotype-tagging single nucleotide polymorphisms (tSNPs) were selected across 21 kb of the IL-6 locus using Haploview software V4.1. The tSNPs were amplified by polymerase chain reaction (PCR) and genotyped by restriction enzyme digestion followed by gel electrophoresis. Linkage disequilibrium (LD) and haplotype reconstruction were carried out by means of a SHEsis program. No distribution difference of any of the five tSNPs between OSAS patients and controls was observed. However, in non-obese individuals (n=117), the minor allele G (rs1800796) decreased risk of OSAS compared with the major allele C [odds ratio (OR), 0.48; 95% confidence interval (CI), 0.26-0.86; p=0.014], and the haplotype TG (rs1880242, rs1800796) conferred a significantly decreased risk of OSAS than single allele G (rs1800796) (OR, 0.39; 95% CI, 0.20-0.74; p=0.003). Moreover, the severity of sleep-disordered breathing (measured by apnea hypopnea index) increased linearly in carriers of the C variant of IL-6 -572G/C polymorphism (14.3+/-5.1, 22.0+/-3.6 and 34.8+/-3.5 for GG, CG and CC, respectively; p=0.012). To the best of our knowledge, this is the first study to suggest that genetic variants in IL-6 could modify OSAS susceptibility. SNP genotyping of IL-6 is a potential strategy for detecting the risk of breathing disordered diseases in non-obese individuals.
Int J Mol Med 2009 Apr
PMID:Genetic variants in interleukin-6 modified risk of obstructive sleep apnea syndrome. 1928 24


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