排序方式: 共有17条查询结果,搜索用时 15 毫秒
1.
2.
3.
The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression 总被引:2,自引:0,他引:2
Org T Chignola F Hetényi C Gaetani M Rebane A Liiv I Maran U Mollica L Bottomley MJ Musco G Peterson P 《EMBO reports》2008,9(4):370-376
Mutations in the gene autoimmune regulator (AIRE) cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. AIRE is expressed in thymic medullary epithelial cells, where it promotes the expression of tissue-restricted antigens. By the combined use of biochemical and biophysical methods, we show that AIRE selectively interacts with histone H3 through its first plant homeodomain (PHD) finger (AIRE-PHD1) and preferentially binds to non-methylated H3K4 (H3K4me0). Accordingly, in vivo AIRE binds to and activates promoters containing low levels of H3K4me3 in human embryonic kidney 293 cells. We conclude that AIRE-PHD1 is an important member of a newly identified class of PHD fingers that specifically recognize H3K4me0, thus providing a new link between the status of histone modifications and the regulation of tissue-restricted antigen expression in thymus. 相似文献
4.
Gompper B Bromundt V Orgül S Flammer J Kräuchi K 《Chronobiology international》2010,27(9-10):1778-1796
The aim of the study was to investigate whether women with primary vascular dysregulation (VD; main symptoms of thermal discomfort with cold extremities) and difficulties initiating sleep (DIS) exhibit a disturbed phase of entrainment (Ψ) under everyday life conditions. The authors predicted a phase delay of the distal-proximal skin temperature gradient and salivary melatonin rhythms with respect to the sleep-wake cycle in women with VD and DIS (WVD) compared to controls (CON), similar to that found in their previous constant-routine laboratory data. A total of 41 young healthy women, 20 with WVD and 21 matched CON without VD and normal sleep onset latency (SOL), were investigated under ambulatory conditions (following their habitual bedtimes) during 7 days of continuous recording of skin temperatures, sleep-wake cycles monitored by actimetry and sleep-wake diaries, and single evening saliva collections for determining the circadian marker of dim light melatonin onset (DLMO). Compared to CON, WVD showed increased distal vasoconstriction at midday and in the evening, as indicated by lower distal (DIST; hands and feet) and foot-calf skin temperatures, and distal-proximal skin temperature gradients (p.05). WVD manifested distal vasoconstriction before lights-off that also lasted longer after lights-off than in CON. In parallel, WVD exhibited a longer SOL (p.05). To define internal phase-relationships, cross-correlation analyses were performed using diurnal rhythms of wrist activity and foot skin temperature. WVD showed a phase delay in foot skin temperature (CON versus WVD: 3.57?±?17.28?min versus 38.50?±?16.65?min; p.05) but not in wrist activity. This finding was validated by additional within-subject cross-correlation analyses using the diurnal wrist activity pattern as reference. DLMO and habitual sleep times did not differ between CON and WVD. The authors conclude that WVD exhibit a phase delay of distal vasodilatation with respect to their habitual sleep-wake cycle and other circadian phase markers, such as DLMO. A full factorial design will have to show whether the finding is specific to primary vascular dysregulation, to DIS, or to their interaction. 相似文献
5.
Long-term (1969–2002) data record of biomass distribution of rotifers in Lake Kinneret is combined with previously published information on their metabolic activity and newly calculated population dynamics parameters to synthesize a model of their seasonal dynamics in Lake Kinneret. Nineteen rotifer species were recorded in routine samples collected in Lake Kinneret (Israel) in 7 offshore (deeper than 5 m), stations, at 12 discrete depths during 1969–2002. Organisms were sorted and counted (including external egg carrying females), biomass was measured and calculated for the entire lake stock (gw.w m−2; mg l−1). Rates of grazing, respiration and production were measured experimentally at three different temperature ranges. Results were extrapolated to the lake community for months with similar temperatures. Rotifera comprised 7% of total zooplankton biomass in Lake Kinneret whilst Cladocera and Copepoda 58 and 35% respectively. Rotifers were found to be more abundant during December–June and decline in summer months. Monthly (1969–2001) means indicated total grazing capacity of rotifers as 11%, respiration as 9% and production as 3.7% of the total zooplankton metabolic activity. Positive relations were indicated between rotifer and small bodied cladoceran numerical concentrations. Population growth models suggest that rotifers are not food limited in Lake Kinneret but that fish predation plays an important role in regulating abundance in spring-summer and fall. 相似文献
6.
Brian W. Parks Elizabeth Nam Elin Org Emrah Kostem Frode Norheim Simon T. Hui Calvin Pan Mete Civelek Christoph D. Rau Brian J. Bennett Margarete Mehrabian Luke K. Ursell Aiqing He Lawrence W. Castellani Bradley Zinker Mark Kirby Thomas A. Drake Christian A. Drevon Aldons J. Lusis 《Cell metabolism》2013,17(1):141-152
- Download : Download high-res image (253KB)
- Download : Download full-size image
7.
Jill C. Gregory Jennifer A. Buffa Elin Org Zeneng Wang Bruce S. Levison Weifei Zhu Matthew A. Wagner Brian J. Bennett Lin Li Joseph A. DiDonato Aldons J. Lusis Stanley L. Hazen 《The Journal of biological chemistry》2015,290(9):5647-5660
Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility. 相似文献
8.
9.
Francesca Chignola Massimiliano Gaetani Ana Rebane Tnis Org Luca Mollica Chiara Zucchelli Andrea Spitaleri Valeria Mannella Prt Peterson Giovanna Musco 《Nucleic acids research》2009,37(9):2951-2961
Plant homeodomain (PHD) fingers are often present in chromatin-binding proteins and have been shown to bind histone H3 N-terminal tails. Mutations in the autoimmune regulator (AIRE) protein, which harbours two PHD fingers, cause a rare monogenic disease, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE activates the expression of tissue-specific antigens by directly binding through its first PHD finger (AIRE-PHD1) to histone H3 tails non-methylated at K4 (H3K4me0). Here, we present the solution structure of AIRE-PHD1 in complex with H3K4me0 peptide and show that AIRE-PHD1 is a highly specialized non-modified histone H3 tail reader, as post-translational modifications of the first 10 histone H3 residues reduce binding affinity. In particular, H3R2 dimethylation abrogates AIRE-PHD1 binding in vitro and reduces the in vivo activation of AIRE target genes in HEK293 cells. The observed antagonism by R2 methylation on AIRE-PHD1 binding is unique among the H3K4me0 histone readers and represents the first case of epigenetic negative cross-talk between non-methylated H3K4 and methylated H3R2. Collectively, our results point to a very specific histone code responsible for non-modified H3 tail recognition by AIRE-PHD1 and describe at atomic level one crucial step in the molecular mechanism responsible for antigen expression in the thymus. 相似文献
10.
Lei Fang Charles Hemion David Goldblum Peter Meyer Selim Orgül Stephan Frank Josef Flammer Albert Neutzner 《PloS one》2012,7(12)