TY - JOUR TI - Transposable elements re-wire and fine-tune the transcriptome. AU - Cowley, M AU - Oakey, RJ AB - What good are transposable elements (TEs)? Although their activity can be harmful to host genomes and can cause disease, they nevertheless represent an important source of genetic variation that has helped shape genomes. In this review, we examine the impact of TEs, collectively referred to as the mobilome, on the transcriptome. We explore how TEs-particularly retrotransposons-contribute to transcript diversity and consider their potential significance as a source of small RNAs that regulate host gene transcription. We also discuss a critical role for the mobilome in engineering transcriptional networks, permitting coordinated gene expression, and facilitating the evolution of novel physiological processes. DA - 2013/// PY - 2013/// DO - 10.1371/journal.pgen.1003234 VL - 9 IS - 1 SP - 1003234 UR - http://europepmc.org/abstract/med/23358118 ER - TY - JOUR TI - PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer AU - Vidal, A. C. AU - Henry, N. M. AU - Murphy, S. K. AU - Oneko, O. AU - Nye, M. AU - Bartlett, J. A. AU - Overcash, F. AU - Huang, Z. AU - Wang, F. AU - Mlay, P. AU - Obure, J. AU - Smith, J. AU - Vasquez, B. AU - Swai, B. AU - Hernandez, B. AU - Hoyo, C. T2 - Clinical and Translational Oncology AB - Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC.We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios.After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations.While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk. DA - 2013/6/18/ PY - 2013/6/18/ DO - 10.1007/S12094-013-1067-4 VL - 16 IS - 3 SP - 266-272 J2 - Clin Transl Oncol LA - en OP - SN - 1699-048X 1699-3055 UR - http://dx.doi.org/10.1007/S12094-013-1067-4 DB - Crossref KW - Insulin-like growth factor 2 gene (IGF2) KW - Paternally expressed gene 1/mesoderm-specific transcript (PEG1/MEST) KW - Human papillomavirus (HPV) KW - Cervical intraepithelial neoplasia (CIN) KW - Invasive cervical cancer (ICC) KW - Differentially methylated regions (DMRs) ER - TY - JOUR TI - Development and Characterization of a Novel Plug and Play Liquid Chromatography-Mass Spectrometry (LC-MS) Source That Automates Connections between the Capillary Trap, Column, and Emitter AU - Bereman, Michael S. AU - Hsieh, Edward J. AU - Corso, Thomas N. AU - Van Pelt, Colleen K. AU - MacCoss, Michael J. T2 - Molecular & Cellular Proteomics AB - We report the development and characterization of a novel, vendor-neutral ultra-high pressure-compatible (~10,000 p.s.i.) LC-MS source. This device is the first to make automated connections with user-packed capillary traps, columns, and capillary emitters. The source uses plastic rectangular inserts (referred to here as cartridges) where individual components (i.e. trap, column, or emitter) can be exchanged independent of one another in a plug and play manner. Automated robotic connections are made between the three cartridges using linear translation powered by stepper motors to axially compress each cartridge by applying a well controlled constant compression force to each commercial LC fitting. The user has the versatility to tailor the separation (e.g. the length of the column, type of stationary phase, and mode of separation) to the experimental design of interest in a cost-effective manner. The source is described in detail, and several experiments are performed to evaluate the robustness of both the system and the exchange of the individual trap and emitter cartridges. The standard deviation in the retention time of four targeted peptides from a standard digest interlaced with a soluble Caenorhabditis elegans lysate ranged between 3.1 and 5.3 s over 3 days of analyses. Exchange of the emitter cartridge was found to have an insignificant effect on the abundance of various peptides. In addition, the trap cartridge can be replaced with minimal effects on retention time (<20 s). DA - 2013/2/19/ PY - 2013/2/19/ DO - 10.1074/MCP.O112.024893 VL - 12 IS - 6 SP - 1701-1708 J2 - Mol Cell Proteomics LA - en OP - SN - 1535-9476 1535-9484 UR - http://dx.doi.org/10.1074/MCP.O112.024893 DB - Crossref ER - TY - JOUR TI - Factors Associated With Adherence to Follow-up Colposcopy AU - Fish, Laura J. AU - Moorman, Patricia G. AU - Wordlaw-Stintson, Lashawn AU - Vidal, Adriana AU - Smith, Jennifer S. AU - Hoyo, Cathrine T2 - American Journal of Health Education AB - Background Understanding the gaps in knowledge about human papilloma virus (HPV) infection, transmission, and health consequences and factors associated with the knowledge gap is an essential first step for the development of interventions to improve adherence to follow-up among women with abnormal Pap smears. Purpose To examine the relationship between knowledge about HPV and adherence to scheduled colposcopic evaluation and variables related to lack of knowledge among women with abnormal Pap tests. Methods Telephone surveys were conducted with women who attended their scheduled appointments (adherers) and women who did not attend their appointments (nonadherers). Results The multivariable analyses indicate that lower HPV knowledge was independently associated with nonadherence to follow-up, controlling for race and education level. Factors related to lower knowledge scores included non-white race, lower education, and lack of health insurance at the time of the scheduled appointment. Conclusion Lack of knowledge of HPV was related to nonadherence among women scheduled for colposcopic evaluation. Translation to Health Education Practice Health education interventions that deliver complex information about HPV and cervical cancer should be in a format that is accessible and understandable to the women who are most at risk of being nonadherent. DA - 2013/11// PY - 2013/11// DO - 10.1080/19325037.2013.838881 VL - 44 IS - 6 SP - 293-298 J2 - American Journal of Health Education LA - en OP - SN - 1932-5037 2168-3751 UR - http://dx.doi.org/10.1080/19325037.2013.838881 DB - Crossref ER - TY - JOUR TI - Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring AU - Vidal, A C AU - Murphy, S K AU - Murtha, A P AU - Schildkraut, J M AU - Soubry, A AU - Huang, Z AU - Neelon, S E B AU - Fuemmeler, B AU - Iversen, E AU - Wang, F AU - Kurtzberg, J AU - Jirtle, R L AU - Hoyo, C T2 - International Journal of Obesity AB - Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations.Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions.After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight.We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations. DA - 2013/3/28/ PY - 2013/3/28/ DO - 10.1038/IJO.2013.47 VL - 37 IS - 7 SP - 907-913 J2 - Int J Obes LA - en OP - SN - 0307-0565 1476-5497 UR - http://dx.doi.org/10.1038/IJO.2013.47 DB - Crossref KW - newborns KW - antibiotics KW - pregnancy KW - birth weight KW - epigenetics KW - race ER - TY - JOUR TI - Vitamin D receptor (VDR) polymorphisms and risk of ovarian cancer in Caucasian and African American women AU - Grant, Delores J. AU - Hoyo, Cathrine AU - Akushevich, Lucy AU - Iversen, Edwin S. AU - Whitaker, Regina AU - Marks, Jeffrey AU - Berchuck, Andrew AU - Schildkraut, Joellen M. T2 - Gynecologic Oncology AB - Polymorphisms in the vitamin D receptor (VDR) gene have been shown in some studies to be associated with the risk of epithelial ovarian cancer (EOC) in Caucasian women. There are no published reports among African Americans.Case-control data from the North Carolina Ovarian Cancer Study were analyzed using logistic regression to determine the association between seven VDR polymorphisms and EOC in both Caucasians (513 cases, 532 controls) and African Americans (74 cases, 79 controls). In a larger sample of African-Americans (125 cases, 155 controls), we assessed associations between six SNPs in proximity of rs7975232.African American women who carried at least one minor allele of rs7975232 were at higher risk for invasive EOC controlling for age and admixture with an odds ratio (OR) for association under the log-additive model of 2.08 (95% confidence interval (CI)=1.19, 3.63, p=0.010). No association was observed between any of the VDR variants and EOC among Caucasians. A larger sample of African Americans revealed a nearly two-fold increased risk of invasive EOC associated with rs7305032, a SNP in proximity to rs7975232 (R(2)=0.369) with a log-additive OR of 1.87 (95% CI=1.20, 2.93, p=0.006).This is the first report showing VDR variants associated with ovarian cancer risk in African American women. A larger study of African American women is needed to confirm these findings. These results imply that vitamin D exposure is a possible modifiable risk factor of ovarian cancer among African Americans. DA - 2013/4// PY - 2013/4// DO - 10.1016/J.YGYNO.2012.12.027 VL - 129 IS - 1 SP - 173-178 J2 - Gynecologic Oncology LA - en OP - SN - 0090-8258 UR - http://dx.doi.org/10.1016/J.YGYNO.2012.12.027 DB - Crossref ER - TY - JOUR TI - DNA methylation at imprint regulatory regions in preterm birth and infection AU - Liu, Ying AU - Hoyo, Cathrine AU - Murphy, Susan AU - Huang, Zhiqing AU - Overcash, Francine AU - Thompson, Jennifer AU - Brown, Haywood AU - Murtha, Amy P. T2 - American Journal of Obstetrics and Gynecology AB - To aid in understanding long-term health consequences of intrauterine infections in preterm birth, we evaluated DNA methylation at 9 differentially methylated regions that regulate imprinted genes by type of preterm birth (spontaneous preterm labor, preterm premature rupture of membranes, or medically indicated [fetal growth restriction and preeclampsia]) and infection status (chorioamnionitis or funisitis).Data on type of preterm birth and infection status were abstracted from medical records and standardized pathology reports in 73 preterm infants enrolled in the Newborn Epigenetics STudy, a prospective cohort study of mother-infant dyads in Durham, NC. Cord blood was collected at birth, and infant DNA methylation levels at the H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 differentially methylated regions were measured using bisulfite pyrosequencing. One-way analyses of variance and logistic regression models were used to compare DNA methylation levels by type of preterm birth and infection status.DNA methylation levels did not differ at any of the regions (P > .20) between infants born via spontaneous preterm labor (average n = 29), preterm premature rupture of membranes (average n = 17), or medically indicated preterm birth (average n = 40). Levels were significantly increased at PLAGL1 in infants with chorioamnionitis (n = 10, 64.4%) compared with infants without chorioamnionitis (n = 63, 57.9%), P < .01. DNA methylation levels were also increased at PLAGL1 for infants with funisitis (n = 7, 63.3%) compared with infants without funisitis (n = 66, 58.3%), P < .05.Dysregulation of PLAGL1 has been associated with abnormal development and cancer. Early-life exposures, including infection/inflammation, may affect epigenetic changes that increase susceptibility to later chronic disease. DA - 2013/5// PY - 2013/5// DO - 10.1016/J.AJOG.2013.02.006 VL - 208 IS - 5 SP - 395.e1-395.e7 J2 - American Journal of Obstetrics and Gynecology LA - en OP - SN - 0002-9378 UR - http://dx.doi.org/10.1016/J.AJOG.2013.02.006 DB - Crossref KW - chorioamnionitis KW - epigenetic KW - funisitis KW - imprinting KW - preterm birth ER - TY - JOUR TI - 75: DNA methylation at imprinted regulatory regions in preterm birth and infection AU - Liu, Ying AU - Hoyo, Cathrine AU - Murphy, Susan AU - Overcash, Francine AU - Thompson, Jennifer AU - Brown, Haywood AU - Murtha, Amy T2 - American Journal of Obstetrics and Gynecology DA - 2013/1// PY - 2013/1// DO - 10.1016/j.ajog.2012.10.240 VL - 208 IS - 1 SP - S45 J2 - American Journal of Obstetrics and Gynecology LA - en OP - SN - 0002-9378 UR - http://dx.doi.org/10.1016/j.ajog.2012.10.240 DB - Crossref ER - TY - JOUR TI - Androgenetic alopecia at various ages and prostate cancer risk in an equal-access multiethnic case–control series of veterans AU - Thomas, Jean-Alfred AU - Antonelli, Jodi A. AU - Banez, Lionel L. AU - Hoyo, Catherine AU - Grant, Delores AU - Demark-Wahnefried, Wendy AU - Platz, Elizabeth A. AU - Gerber, Leah AU - Shuler, Kathryn AU - Eyoh, Enwono AU - Calloway, Elizabeth AU - Freedland, Stephen J. T2 - Cancer Causes & Control AB - Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. We performed a case–control study at a Veterans Affairs Hospital among 708 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30 and 40 and at study enrollment. We tested the association between hair pattern (overall, vertex, or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome. Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p = 0.008). Similar patterns were noted for frontal (p = 0.005) and not vertex balding (p = 0.22). When compared with biopsy-negative men, a similar pattern was seen with younger age of AA onset having higher risk of CaP, though this was not significant (p = 0.07). A suggestion for younger age of AA onset for frontal (p = 0.07) being associated with CaP versus biopsy-negative men was also observed. Overall balding (yes/no) was associated with greater than twofold increase in high-grade disease (p = 0.02). Men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology. DA - 2013/3/26/ PY - 2013/3/26/ DO - 10.1007/S10552-013-0182-4 VL - 24 IS - 5 SP - 1045-1052 J2 - Cancer Causes Control LA - en OP - SN - 0957-5243 1573-7225 UR - http://dx.doi.org/10.1007/S10552-013-0182-4 DB - Crossref ER - TY - JOUR TI - Association between exercise and primary incidence of prostate cancer AU - Singh, Abhay A. AU - Jones, Lee W. AU - Antonelli, Jodi A. AU - Gerber, Leah AU - Calloway, Elizabeth E. AU - Shuler, Kathleen H. AU - Freedland, Stephen J. AU - Grant, Delores J. AU - Hoyo, Cathrine AU - Bañez, Lionel L. T2 - Cancer AB - Exercise is a modifiable lifestyle risk factor associated with prostate cancer risk reduction. However, whether this association is different as a function of race is unclear. In the current study, the authors attempted to characterize the link between exercise and prostate cancer (CaP) in white and black American men.Using a prospective design, 307 men (164 of whom were white and 143 of whom were black) who were undergoing prostate biopsy completed a self-reported survey that assessed exercise behavior (metabolic equivalent [MET] hours per week). Crude and adjusted logistic regression analyses were used to estimate the risk of prostate cancer controlling for age, body mass index, digital rectal examination findings, previous biopsy, Charlson comorbidity score, and family history of CaP stratified by self-reported race.There was no significant difference noted with regard to the amount of exercise between racial groups (P = .12). Higher amounts of MET hours per week were associated with a decreased risk of CaP for white men in both crude (P = .02) and adjusted (P = .04) regression models. Among whites, men who exercised ≥ 9 MET hours per week were less likely to have a positive biopsy result compared with men exercising < 9 MET hours per week (odds ratio, 0.47; 95% confidence interval, 0.22-0.99 [P = .047]). There was no association noted between MET hours per week and risk of CaP among black men in both crude (P = .79) and adjusted (P = .76) regression models.In a prospective cohort of men undergoing biopsy, increased exercise, measured as MET hours per week, was found to be associated with CaP risk reduction among white but not black men. Investigating race-specific mechanisms by which exercise modifies CaP risk and why these mechanisms disfavor black men in particular are warranted. DA - 2013/2/11/ PY - 2013/2/11/ DO - 10.1002/CNCR.27791 VL - 119 IS - 7 SP - 1338-1343 J2 - Cancer LA - en OP - SN - 0008-543X UR - http://dx.doi.org/10.1002/CNCR.27791 DB - Crossref KW - prostate neoplasms KW - exercise KW - continental population groups KW - core needle biopsy KW - male ER - TY - JOUR TI - Newborns of obese parents have altered DNA methylation patterns at imprinted genes AU - Soubry, A AU - Murphy, S K AU - Wang, F AU - Huang, Z AU - Vidal, A C AU - Fuemmeler, B F AU - Kurtzberg, J AU - Murtha, A AU - Jirtle, R L AU - Schildkraut, J M AU - Hoyo, C T2 - International Journal of Obesity AB - Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity.We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT).We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ⩾30 kg m(-2), was ascertained through standardized questionnaires.After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β=-2.57; s.e.=0.95; P=0.008), PEG3 (β=-1.71; s.e.=0.61; P=0.005) and NNAT (β=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: β-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR.We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood. DA - 2013/10/25/ PY - 2013/10/25/ DO - 10.1038/IJO.2013.193 VL - 39 IS - 4 SP - 650-657 J2 - Int J Obes LA - en OP - SN - 0307-0565 1476-5497 UR - http://dx.doi.org/10.1038/IJO.2013.193 DB - Crossref ER -