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Replication, Repair, and Reactivation

Matthew W. Vaughn, Milos Tanurdzic, Rob Martienssen
2005 Developmental Cell  
Shelterin consists of a half-dozen proteins that together bind to telomere repeats and fold them into an interesting Matthew W.  ...  Vaughn, Milos Tanurdzic, and Rob Martienssen Cold Spring Harbor Laboratory 1 Bungtown Road Cold Spring Harbor, New York 11724  ... 
doi:10.1016/j.devcel.2005.11.011 pmid:16326383 fatcat:kgybaefq7bayncfrfvyqq5cnse

Hidden Obesity in Dialysis Patients: Clinical Implications

Matthew K. Abramowitz, Deep Sharma, Vaughn W. Folkert
2016 Seminars in dialysis  
While body-mass index (BMI) is used to diagnose obesity in the general population, its application in the end-stage renal disease (ESRD) population is fraught with difficulty. A major limitation is its inability to distinguish muscle mass from fat mass, thereby leading to misclassification of individuals with poor muscle mass but excess adipose tissue as non-obese (i.e. BMI <30 kg/m 2 ). As muscle wasting is common among ESRD patients, this is an important problem. A substantial proportion of
more » ... RD patients have levels of BMI in the normal range, yet excess adiposity based on other measures. The importance of this "hidden" obesity remains to be determined, but it must be recognized in order for obesity interventions to be appropriately targeted and tested in the ESRD population.
doi:10.1111/sdi.12516 pmid:27144783 pmcid:PMC5014614 fatcat:lo3kv2mwdzbfxa44imroeyr77y

Repliscan: a tool for classifying replication timing regions [article]

Gregory J Zynda, Jawon Song, Lorenzo Concia, Emily E Wear, Linda Hanley-Bowdoin, William F Thompson, Matthew W Vaughn
2016 bioRxiv   pre-print
C ct (w) =    1, if S ct (w) > 0.5, 0, otherwise (20) The infinity-norm ensures that the largest value will always be classified as replicating, and this classification method allows for a window to  ...  S ct (w) = R cwt R cw ∞ (19) This operation scales the largest value to 1 and the others to the range [0,1].  ... 
doi:10.1101/094177 fatcat:rmyvbczujrdt3o2lwizzyeaxaq

Finding the Right Template: RNA Pol IV, a Plant-Specific RNA Polymerase

Matthew W. Vaughn, Robert A. Martienssen
2005 Molecular Cell  
An explanation may be found in the silencing pheno-Matthew W. Vaughn and Robert A. Martienssen type of mutants in Pol IV.  ... 
doi:10.1016/j.molcel.2005.03.003 pmid:15780931 fatcat:l6lihvvzfbhnzfo4ekkizvgjse

Epigenomic Consequences of Immortalized Plant Cell Suspension Culture

Milos Tanurdzic, Matthew W Vaughn, Hongmei Jiang, Tae-Jin Lee, R. Keith Slotkin, Bryon Sosinski, William F Thompson, R. W Doerge, Robert A Martienssen, Wolf Reik
2008 PLoS Biology  
Citation: Tanurdzic M, Vaughn MW, Jiang H, Lee TJ, Slotkin RK, et al. (2008) Epigenomic consequences of immortalized plant cell suspension culture. PLoS Biol 6(12): e302.  ...  W. McCombie, Melissa delaBastide, and Danea Rebolini for their help with small RNA sequencing. We thank our colleagues Linda Hanley-Bowdoin and George Allen for discussions. Author Funding.  ...  thaliana, ecotype Columbia, were cut out 7 d after plating on MS plates and transferred onto 13 MS plates supplemented with auxin and cytokinin (0.15 lg/ml IAA and 0.625 lg/ml isopentanyladenine) and 3% (w/  ... 
doi:10.1371/journal.pbio.0060302 pmid:19071958 pmcid:PMC2596858 fatcat:47z2qlk6t5f5ddexvy57nmjkty

Lid2 Is Required for Coordinating H3K4 and H3K9 Methylation of Heterochromatin and Euchromatin

Fei Li, Maite Huarte, Mikel Zaratiegui, Matthew W. Vaughn, Yang Shi, Rob Martienssen, W. Zacheus Cande
2008 Cell  
In most eukaryotes, histone methylation patterns regulate chromatin architecture and function: methylation of histone H3 lysine-9 (H3K9) demarcates heterochromatin, whereas H3K4 methylation demarcates euchromatin. We show here that the S. pombe JmjC-domain protein Lid2 is a trimethyl H3K4 demethylase responsible for H3K4 hypomethylation in heterochromatin. Lid2 interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/ Clr8-Rik1 complex, which also functions in the RNA
more » ... erence pathway. Disruption of the JmjC domain alone results in severe heterochromatin defects and depletion of siRNA, whereas overexpressing Lid2 enhances heterochromatin silencing. The physical and functional link between H3K4 demethylation and H3K9 methylation suggests that the two reactions act in a coordinated manner. Surprisingly, crossregulation of H3K4 and H3K9 methylation in euchromatin also requires Lid2. We suggest that Lid2 enzymatic activity in euchromatin is regulated through a dynamic interplay with other histone-modification enzymes. Our findings provide mechanistic insight into the coordination of H3K4 and H3K9 methylation.
doi:10.1016/j.cell.2008.08.036 pmid:18957202 pmcid:PMC2614271 fatcat:bcxfbtp7izgsbji7ux7hgt6yce

Repliscan: a tool for classifying replication timing regions

Gregory J. Zynda, Jawon Song, Lorenzo Concia, Emily E. Wear, Linda Hanley-Bowdoin, William F. Thompson, Matthew W. Vaughn
2017 BMC Bioinformatics  
C ct (w) =    1, if S ct (w) > 0.5, 0, otherwise (20) The infinity-norm ensures that the largest value will always be classified as replicating, and this classification method allows for a window to  ...  S ct (w) = R cwt R cw ∞ (19) This operation scales the largest value to 1 and the others to the range [0,1].  ... 
doi:10.1186/s12859-017-1774-x pmid:28784090 pmcid:PMC5547489 fatcat:nm2dysfphbewnp3pu3nuj57hta

Epigenetic Natural Variation in Arabidopsis thaliana

Matthew W Vaughn, Miloš Tanurdžić, Zachary Lippman, Hongmei Jiang, Robert Carrasquillo, Pablo D Rabinowicz, Neilay Dedhia, W. Richard McCombie, Nicolas Agier, Agnès Bulski, Vincent Colot, R.W Doerge (+2 others)
2007 PLoS Biology  
Cytosine methylation of repetitive sequences is widespread in plant genomes, occurring in both symmetric (CpG and CpNpG) as well as asymmetric sequence contexts. We used the methylation-dependent restriction enzyme McrBC to profile methylated DNA using tiling microarrays of Arabidopsis Chromosome 4 in two distinct ecotypes, Columbia and Landsberg erecta. We also used comparative genome hybridization to profile copy number polymorphisms. Repeated sequences and transposable elements (TEs),
more » ... lly long terminal repeat retrotransposons, are densely methylated, but one third of genes also have low but detectable methylation in their transcribed regions. While TEs are almost always methylated, genic methylation is highly polymorphic, with half of all methylated genes being methylated in only one of the two ecotypes. A survey of loci in 96 Arabidopsis accessions revealed a similar degree of methylation polymorphism. Within-gene methylation is heritable, but is lost at a high frequency in segregating F 2 families. Promoter methylation is rare, and gene expression is not generally affected by differences in DNA methylation. Small interfering RNA are preferentially associated with methylated TEs, but not with methylated genes, indicating that most genic methylation is not guided by small interfering RNA. This may account for the instability of gene methylation, if occasional failure of maintenance methylation cannot be restored by other means.
doi:10.1371/journal.pbio.0050174 pmid:17579518 pmcid:PMC1892575 fatcat:2r25uh5ibbdfvnlceklgrssine

Role of transposable elements in heterochromatin and epigenetic control

Zachary Lippman, Anne-Valérie Gendrel, Michael Black, Matthew W. Vaughn, Neilay Dedhia, W. Richard McCombie, Kimberly Lavine, Vivek Mittal, Bruce May, Kristin D. Kasschau, James C. Carrington, Rebecca W. Doerge (+2 others)
2004 Nature  
proteins were removed by washing the beads six times with high ionic strength buffer. Bound protein was eluted with electrophoresis sample buffer containing 1% SDS, 2.5% 2-mercaptoethanol, 0.063 M Tris-HCl (pH 6.8) and 15% glycerol, and resolved by 6% or 8% SDS-PAGE. Western blot analysis was carried out with antisera against mPER2 (ref. 1), NPAS2 (ref. 10) and GAPDH (Sigma). Bound antibodies were detected by Supersignal West Pico Chemiluminescent Substrate (Pierce). Cyanocobalamin (335 mM) was
more » ... added to the binding solution for competition studies.
doi:10.1038/nature02651 pmid:15269773 fatcat:tapmgwx6kzbarh3j25onsj4scq


Frances Vaughn Wilder, Paul E. Leaverton, Matthew W. Rogers, Nancy B. Lemrow
2009 Journal of Musculoskeletal Research  
Objective: To evaluate the association between vitamin supplements and the incidence and progression of radiographic knee osteoarthritis (OA). Study Design: Prospective cohort. Methods: Men and women aged 40 years and older (N = 2239) participating in the community-based Clearwater Osteoarthritis Study (1988-current) with biennial, sequential radiographs. The Lawrence & Kellgren ordinal scale was used to determine evidence of the study outcome, radiographic knee OA, and progression of
more » ... ic knee OA. The study exposure was baseline history of self-reported vitamin supplement usage. Results: Individuals without baseline knee OA who self-reported vitamin supplement usage were 12% less likely to develop knee OA than were those individuals who self-reported no vitamin supplement usage (RR = 0.88; 95% C.I. 0.86-0.89). Those with baseline knee OA who self-reported vitamin supplement usage were 7% less likely to experience knee OA progression than were those individuals who self-reported no vitamin supplement usage (RR = 0.93; 95% C.I. 0.87-0.99 ). Conclusion: After consideration of BMI, gender, age, history of knee trauma, exercise and vitamin supplement usage prior to study baseline, these findings suggest that vitamin supplement usage may play a protective role in knee OA. Vitamin supplements may be a cost-effective strategy to reduce the incidence Correspondence to: . 85 J. Musculoskelet. Res. 2009.12:85-93. Downloaded from by Dr. Lissa Fahlman on 10/09/12. For personal use only. 86 F. V. Wilder et al. and/or slow the progression of knee OA. As many approved OA drugs are accompanied by adverse side effects, the role of vitamin supplements in the development and progression of knee OA warrants further investigation.
doi:10.1142/s0218957709002274 fatcat:hfu4zblybfelzkkxzk6iyant2a

Variation in DNA Methylation Patterns is More Common among Maize Inbreds than among Tissues

Steven R. Eichten, Matthew W. Vaughn, Peter J. Hermanson, Nathan M. Springer
2013 The Plant Genome  
Heynh. have found DNA methylation differences among ecotypes (Vaughn et al., 2007) and in spontaneous mutant accumulation lines (Becker et al., 2011; Schmitz and Ecker, 2012) .  ... 
doi:10.3835/plantgenome2012.06.0009 fatcat:vdlxsfdyoja7jkbcjdk3qrjrsq

CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR

Mikel Zaratiegui, Matthew W. Vaughn, Danielle V. Irvine, Derek Goto, Stephen Watt, Jürg Bähler, Benoit Arcangioli, Robert A. Martienssen
2010 Nature  
doi:10.1038/nature09608 pmid:21151105 pmcid:PMC3057531 fatcat:vz4r5dfpsjewvpxfhf5dccqkoa

Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding RNAs

Matthew J. Hangauer, Ian W. Vaughn, Michael T. McManus, John L. Rinn
2013 PLoS Genetics  
Known protein coding gene exons compose less than 3% of the human genome. The remaining 97% is largely uncharted territory, with only a small fraction characterized. The recent observation of transcription in this intergenic territory has stimulated debate about the extent of intergenic transcription and whether these intergenic RNAs are functional. Here we directly observed with a large set of RNA-seq data covering a wide array of human tissue types that the majority of the genome is indeed
more » ... nscribed, corroborating recent observations by the ENCODE project. Furthermore, using de novo transcriptome assembly of this RNA-seq data, we found that intergenic regions encode far more long intergenic noncoding RNAs (lincRNAs) than previously described, helping to resolve the discrepancy between the vast amount of observed intergenic transcription and the limited number of previously known lincRNAs. In total, we identified tens of thousands of putative lincRNAs expressed at a minimum of one copy per cell, significantly expanding upon prior lincRNA annotation sets. These lincRNAs are specifically regulated and conserved rather than being the product of transcriptional noise. In addition, lincRNAs are strongly enriched for trait-associated SNPs suggesting a new mechanism by which intergenic trait-associated regions may function. These findings will enable the discovery and interrogation of novel intergenic functional elements.
doi:10.1371/journal.pgen.1003569 pmid:23818866 pmcid:PMC3688513 fatcat:okuvfttgp5dbjfjf7oqelvxmsu

Variability in monthly serum bicarbonate measures in hemodialysis patients: a cohort study

Ravi Patel, William Paredes, Charles B. Hall, Mark A. Nader, Deepak Sapkota, Vaughn W. Folkert, Matthew K. Abramowitz
2015 BMC Nephrology  
Some nephrologists have advocated an individualized approach to the prescription of bicarbonate hemodialysis. However, the utility of monthly serum bicarbonate levels for guiding and evaluating such treatment decisions has not been evaluated. We sought to define the variability of these measurements and to determine factors that are associated with month-to-month variability in pre-dialysis serum bicarbonate. Methods: We examined the monthly variability in serum bicarbonate measurements among
more » ... 1 hemodialysis patients admitted to a free-standing dialysis unit in the Bronx, NY from 1/1/2008-6/30/2012. All patients were treated with a uniform bicarbonate dialysis prescription (bicarbonate 35 mEq/L, acetate 8 mEq/L). Pre-dialysis serum bicarbonate values were obtained from monthly laboratory reports. Month-to-month variability was defined using a rolling measurement for each time point. Results: Only 34 % of high serum bicarbonate values (>26 mEq/L) remained high in the subsequent month, whereas 60 % converted to normal (22-26 mEq/L). Of all low values (<22 mEq/L), 41 % were normal the following month, while 58 % remained low. Using the mean 3-month bicarbonate, only 29 % of high values remained high in the next 3-month period. In multivariable-adjusted longitudinal models, both low and high serum bicarbonate values were associated with greater variability than were normal values (β = 0.12 (95 % CI 0.09-0.15) and 0.24 (0.18 to 0.29) respectively). Variability decreased with time, and was significantly associated with age, phosphate binder use, serum creatinine, potassium, and normalized protein catabolic rate. Conclusions: Monthly pre-dialysis serum bicarbonate levels are highly variable. Even if a clinician takes no action, approximately 50 % of bicarbonate values outside a normal range of 22-26 mEq/L will return to normal in the subsequent month. The decision to change the bicarbonate dialysis prescription should not be based on a single bicarbonate value, and even a 3-month mean may be insufficient.
doi:10.1186/s12882-015-0206-2 pmid:26689440 pmcid:PMC4687073 fatcat:biwqq5cle5cxbaavpf5a5u4vwq

The Fission Yeast Jmj2 Reverses Histone H3 Lysine 4 Trimethylation

Maite Huarte, Fei Lan, Taesoo Kim, Matthew W. Vaughn, Mikel Zaratiegui, Robert A. Martienssen, Stephen Buratowski, Yang Shi
2007 Journal of Biological Chemistry  
Histone methylation regulates transcription, chromatin structure, and the epigenetic state of the cell. Recent studies identified the JmjC domain as a catalytic module for histone demethylation. Schizosaccharomyces pombe contains seven JmjC proteins, but it was unclear whether any of them functioned as histone demethylases. In this report, we show that the JmjC protein Jmj2, which is evolutionarily conserved from yeast to human, reversed trimethylated H3-Lys-4 to di-and monobut not unmethylated
more » ... products. Overexpression of Jmj2 but not a catalytically inactive mutant reduced H3-Lys-4 trimethylation levels in vivo and suppressed the toxicity caused by overexpression of the H3-Lys-4-me3-binding protein Yng1 in budding yeast. Genome-wide analysis showed that the loss of jmj2 was associated with an increase in the H3-Lys-4-me3 signal, which was enriched near the transcriptional start sites and the coding regions. At the mating-type locus, the loss of jmj2 or substitution of jmj2 with a catalytically inactive form is correlated with increased reporter gene transcription and H3-Lys-4-me3/2 levels, suggesting that Jmj2 and its demethylase activity may play a role in heterochromatin biology. Our findings identified a novel S. pombe histone demethylase with specificity toward di-and trimethylated histone H3-Lys-4 and a possible role in heterochromatin regulation.
doi:10.1074/jbc.m703897200 pmid:17550896 fatcat:rvpq4eazu5gezophuhwy7gzxlu
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