Nucleosomes
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Methods in enzymology, ISSN 0076-6879 Vol. 170
XXIX, 683 s. : il. ; 24 cm
High resolution sequence-directed nucleosome mapping is applied to 36,000 sequences containing splice junctions, from five different species. As it has been also shown in previous studies, the junctions are found to be preferentially located within nucleosomes. Moreover, the orientation of guanine residues at the GT- and AG-ends of introns within the nucleosomes is such that the guanines are positioned nearest to the surface of histone octamers, 3 and 4 bases upstream from the local DNA pseudo-dyads passing through minor grooves oriented outwards. Since the guanine residues are the most vulnerable to spontaneous damage within the cell (primarily, depurination and oxidation) such positioning of the splice junctions minimizes the damage that is caused by free radicals and highly reactive metabolites.
- MeSH
- dánio pruhované genetika MeSH
- histony metabolismus MeSH
- introny MeSH
- kur domácí genetika MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- myši MeSH
- nukleozomy genetika MeSH
- psi MeSH
- sekvence nukleotidů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Chromatin Assembly Factor 1 (CAF-1) is a major nucleosome assembly complex which functions particularly during DNA replication and repair. Here we studied how the nucleosome landscape changes in a CAF-1 mutant in the model plant Arabidopsis thaliana. Globally, most nucleosomes were not affected by loss of CAF-1, indicating the presence of efficient alternative nucleosome assemblers. Nucleosomes that we found depleted in the CAF-1 mutant were enriched in non-transcribed regions, consistent with the notion that CAF-1-independent nucleosome assembly can compensate for loss of CAF-1 mainly in transcribed regions. Depleted nucleosomes were particularly enriched in proximal promoters, suggesting that CAF-1-independent nucleosome assembly mechanisms are often not efficient upstream of transcription start sites. Genes related to plant defense were particularly prone to lose nucleosomes in their promoters upon CAF-1 depletion. Reduced nucleosome occupancy at promoters of many defense-related genes is associated with a primed gene expression state that may considerably increase plant fitness by facilitating plant defense. Together, our results establish that the nucleosome landscape in Arabidopsis is surprisingly robust even in the absence of the dedicated nucleosome assembly machinery CAF-1 and that CAF-1-independent nucleosome assembly mechanisms are less efficient in particular genome regions.
- MeSH
- Arabidopsis genetika imunologie metabolismus MeSH
- chromatin genetika MeSH
- faktor 1 pro uspořádání chromatinu genetika metabolismus MeSH
- imunita rostlin genetika MeSH
- mutace MeSH
- nukleozomy genetika metabolismus MeSH
- oprava DNA genetika MeSH
- počátek transkripce MeSH
- promotorové oblasti (genetika) genetika MeSH
- replikace DNA genetika MeSH
- restrukturace chromatinu genetika MeSH
- sekvenční analýza DNA MeSH
- Publikační typ
- časopisecké články MeSH
Psoriasis is a multifactorial chronic inflammatory disease. We aimed to examine blood levels of nucleosomes derived from apoptotic cells, nucleosomal cell-free DNA (cfDNA) and immune-inflammatory biomarkers tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6) in psoriatic subjects. The study included 28 patients with exacerbated psoriasis vulgaris and 22 controls. The clinical and laboratory investigations included the determination of PASI score, BMI, cfDNA (by real-time PCR), nucleosomes, TNF-α, CRP, and IL-6. The range of PASI score in psoriatic patients was 10-34 (median 19). In the patients, we found significantly elevated levels (p < 0.001) of cfDNA, nucleosomes, TNF-α, CRP, and IL-6. We did not find any significant relationship between the analyzed parameters in either group (i.e., experimental or control). Elevated levels of the biomarkers of inflammation (TNF-α, CRP, and IL-6) and the indicators of apoptosis (cfDNA, circulating nucleosomes) proved that exacerbated psoriasis vulgaris is associated with a high degree of systemic inflammatory responses and dysregulated apoptotic pathways.
- MeSH
- apoptóza MeSH
- biologické markery krev MeSH
- C-reaktivní protein analýza MeSH
- dospělí MeSH
- interleukin-6 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nukleozomy genetika metabolismus MeSH
- progrese nemoci MeSH
- psoriáza krev patologie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- TNF-alfa krev MeSH
- volné cirkulující nukleové kyseliny krev MeSH
- zánět MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- biologické markery krev MeSH
- buněčná smrt fyziologie MeSH
- lidé MeSH
- nukleozomy metabolismus MeSH
- psoriáza krev terapie MeSH
- pyreny moč MeSH
- terapie ultrafialovými paprsky metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
OBJECTIVE: While circulating nucleosome levels are high in obese mouse models, it is unknown where these nucleosomes originate from and whether they are a marker of cardio-metabolic health in humans. Here, we aimed to determine whether an association exists between circulating nucleosomes and the risk of developing obesity, metabolic syndrome (MetS) and/or a dysfunctional cardiovascular performance. METHODS: We randomly selected 120 participants of the Kardiovize Brno 2030 study across three BMI strata: BMI 18-25, 25-30, and > 30. We assessed the association between circulating nucleosome levels and the risk of obesity, MetS, and poor cardiovascular health. We then cultured human neutrophils, adipocytes, and hepatoma cells to study nucleosome origins in a fat-rich environment. RESULTS: Circulating nucleosome levels positively correlated with BMI (R = 0.602, p < 0.05), fatty liver index (R = 0.622, p < 0.05), left ventricular mass (R = 0.457, p < 0.05), and associated with MetS (p < 0.001) and poor cardiovascular health (p < 0.001). Incubating neutrophils with 1-10 μM free fatty acids triggered nucleosome production without concomitant cell death. Nucleosomes were not produced during pre-adipocyte differentiation or upon incubation of hepatic cells with palmitic acid. CONCLUSIONS: Neutrophils are a bona fide source of circulating nucleosomes in an obesogenic environment and in overweight/obese patients. High nucleosome levels are associated with MetS and cardiovascular performance, and might represent novel candidate biomarkers for cardio-metabolic health.
- MeSH
- buňky Hep G2 MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- kardiovaskulární nemoci etiologie MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom krev komplikace MeSH
- nadváha krev komplikace metabolismus MeSH
- neutrofily cytologie metabolismus MeSH
- nukleozomy metabolismus MeSH
- obezita krev komplikace metabolismus MeSH
- senioři MeSH
- tukové buňky cytologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
