Table of Contents

Volume 7, Issue 6

  June 2012

  Pages 525 - 668

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EDITOR'S PREVIEW

Open Access Article

In this issue of Epigenetics

Barbara P. Rattner
Pages 525 - 527
http://dx.doi.org/10.4161/epi.20589
Full Text | PDF




BRIEF REPORTS

Virion-mediated transfer of SV40 epigenetic information

Barry Milavetz, Les Kallestad, Amanda Gefroh, Nicholas Adams, Emily Woods and Lata Balakrishnan
Pages 528 - 534
http://dx.doi.org/10.4161/epi.20057
Abstract | Full Text | PDF

In eukaryotes, epigenetic information can be encoded in parental cells through modification of histones and subsequently passed on to daughter cells in a process known as transgenerational epigenetic regulation. Simian Virus 40 (SV40) is a well-characterized virus whose small circular DNA genome is organized into chromatin and, as a consequence, undergoes many of the same biological processes observed in cellular chromatin. In order to determine whether SV40 is capable of transgenerational epigenetic regulation, we have analyzed SV40 chromatin from minichromosomes and virions for the presence of modified histones using various ChIP techniques and correlated these modifications with specific biological effects on the SV40 life cycle. Our results demonstrate that, like its cellular counterpart, SV40 chromatin is capable of passing biologically relevant transgenerational epigenetic information between infections.

A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia

Nicholas C. Wong, David Ashley, Zac Chatterton, Mandy Parkinson-Bates, Hong Kiat Ng, Minhee S. Halemba, Adam Kowalczyk, Justin Bedo, Qiao Wang, Katrina Bell, Elizabeth Algar, Jeffrey M Craig and Richard Saffery
Pages 535 - 541
http://dx.doi.org/10.4161/epi.20193
Abstract | Full Text | PDF

Pre-B cell acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy and remains one of the highest causes of childhood mortality. Despite this, the mechanisms leading to disease remain poorly understood. We asked if recurrent aberrant DNA methylation plays a role in childhood ALL and have defined a genome-scale DNA methylation profile associated with the ETV6-RUNX1 subtype of pediatric ALL. Archival bone marrow smears from 19 children collected at diagnosis and remission were used to derive a disease specific DNA methylation profile. The gene signature was confirmed in an independent cohort of 86 patients. A further 163 patients were analyzed for DNA methylation of a three gene signature. We found that the DNA methylation signature at diagnosis was unique from remission. Fifteen loci were sufficient to discriminate leukemia from disease-free samples and purified CD34+ cells. DNA methylation of these loci was recurrent irrespective of cytogenetic subtype of pre-B cell ALL. We show that recurrent aberrant genomic methylation is a common feature of pre-B ALL, suggesting a shared pathway for disease development. By revealing new DNA methylation markers associated with disease, this study has identified putative targets for development of novel epigenetic-based therapies.




RESEARCH PAPERS

Open Access Article

Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient

Holger Heyn, Enrique Vidal, Sergi Sayols, Jose V. Sanchez-Mut, Sebastian Moran, Ignacio Medina, Juan Sandoval, Laia Simó-Riudalbas, Karolina Szczesna, Dori Huertas, Sole Gatto, Maria R. Matarazzo, Joaquin Dopazo and Manel Esteller
Pages 542 - 550
http://dx.doi.org/10.4161/epi.20523
Abstract | Full Text | PDF

The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is associated to mutations of the DNA methyl-transferase DNMT3B, resulting in a reduction of enzyme activity. Aberrant expression of immune system genes and hypomethylation of pericentromeric regions accompanied by chromosomal instability were determined as alterations driving the disease phenotype. However, so far only technologies capable to analyze single loci were applied to determine epigenetic alterations in ICF patients. In the current study, we performed whole-genome bisulphite sequencing to assess alteration in DNA methylation at base pair resolution. Genome-wide we detected a decrease of methylation level of 42%, with the most profound changes occurring in inactive heterochromatic regions, satellite repeats and transposons. Interestingly, transcriptional active loci and ribosomal RNA repeats escaped global hypomethylation. Despite a genome-wide loss of DNA methylation the epigenetic landscape and crucial regulatory structures were conserved. Remarkably, we revealed a mislocated activity of mutant DNMT3B to H3K4me1 loci resulting in hypermethylation of active promoters. Functionally, we could associate alterations in promoter methylation with the ICF syndrome immunodeficient phenotype by detecting changes in genes related to the B-cell receptor mediated maturation pathway.

Silencing of Wnt5a during colon cancer metastasis involves histone modifications

Qian Li and Hong Chen
Pages 551 - 558
http://dx.doi.org/10.4161/epi.20050
Abstract | Full Text | PDF

Colorectal cancer (CRC) is the third most common cancer in the United States. Approximately 90% of colon cancer deaths arise from the metastasis of primary tumors. Aberrant expression of Wnt5a, one of the WNT signaling factors, has been reported during colon cancer development and progression. We found that both mRNA and protein expression of Wnt5a were decreased in the highly metastatic human colon cancer cell line SW620 compared with the non-metastatic human colon cancer cell SW480. This study tested the hypothesis that the silencing of Wnt5a in metastatic human colon cancer cells is related to altered epigenetic modifications. Wnt5a expression was not responsive to DNA methyltransferase inhibitor 5-aza-cytidine treatment. However, histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate (NaBt) significantly increased Wnt5a mRNA expression in SW620. Importantly, lower transcription of Wnt5a in SW620 than SW480 corresponded to multiple histone modifications, including lower levels of acetylated histone H3, H4 and H3K4me2 and higher levels of H3K27me3 in the promoter region. The increase of H3Ac, H4Ac and H3K4me2 after NaBt treatment in SW620 confirmed the involvement of histone modifications in the transcriptional regulation of Wnt5a. Additionally, NaBt treatment increased β-catenin signaling and diminished the difference in cell adhesion ability between non-metastatic SW480 and metastatic SW620, suggesting that the HDAC inhibitor plays critical roles in the WNT signaling pathway and cell physiology that relate to metastasis. In conclusion, our study suggests the importance of Wnt5a in colon cancer metastasis and also indicates that Wnt5a silencing in the highly invasive human colon cancer cell line might result from transcriptional regulation of the gene by histone modifications.

Key epigenetic changes associated with lung cancer development: Results from dense methylation array profiling

Heather H. Nelson, Carmen J. Marsit, Brock C. Christensen, E. Andres Houseman, Milica Kontic, Joseph L. Wiemels, Margaret R. Karagas, Margaret R. Wrensch, Shichun Zheng, John K. Wiencke and Karl T. Kelsey
Pages 559 - 566
http://dx.doi.org/10.4161/epi.20219
Abstract | Full Text | PDF

Epigenetic alterations are a common event in lung cancer and their identification can serve to inform on the carcinogenic process and provide clinically relevant biomarkers. Using paired tumor and non-tumor lung tissues from 146 individuals from three independent populations we sought to identify common changes in DNA methylation associated with the development of non-small cell lung cancer. Pathologically normal lung tissue taken at the time of cancer resection was matched to tumorous lung tissue and together were probed for methylation using Illumina GoldenGate arrays in the discovery set (n = 47 pairs) followed by bisulfite pyrosequencing for validation sets (n = 99 pairs). For each matched pair the change in methylation at each CpG was calculated (the odds ratio), and these ratios were averaged across individuals and ranked by magnitude to identify the CpGs with the greatest change in methylation associated with tumor development. We identified the top gene-loci representing an increase in methylation (HOXA9, 10.3-fold and SOX1, 5.9-fold) and decrease in methylation (DDR1, 8.1-fold). In replication testing sets, methylation was higher in tumors for HOXA9 (p < 2.2 × 10⁻¹⁶) and SOX1 (p < 2.2 × 10⁻¹⁶) and lower for DDR1 (p < 2.2 × 10⁻¹⁶). The magnitude and strength of these changes were consistent across squamous cell and adenocarcinoma tumors. Our data indicate that the identified genes consistently have altered methylation in lung tumors. Our identified genes should be included in translational studies that aim to develop screening for early disease detection.

Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemia

Lirong Pei, Jeong-Hyeon Choi, Jimei Liu, Eun-Joon Lee, Brian McCarthy, James M. Wilson, Ethan Speir, Farrukh Awan, Hongseok Tae, Gerald Arthur, Jennifer L. Schnabel, Kristen H. Taylor, Xinguo Wang, Dong Xu, Han-Fei Ding, David H. Munn, Charles Caldwell and Huidong Shi
Pages 567 - 578
http://dx.doi.org/10.4161/epi.20237
Abstract | Full Text | PDF

We conducted a genome-wide DNA methylation analysis in CD19⁺ B-cells from chronic lymphocytic leukemia (CLL) patients and normal control samples using reduced representation bisulfite sequencing (RRBS). The methylation status of 1.8–2.3 million CpGs in the CLL genome was determined; about 45% of these CpGs were located in more than 23,000 CpG islands (CGIs). While global CpG methylation was similar between CLL and normal B-cells, 1764 gene promoters were identified as being differentially methylated in at least one CLL sample when compared with normal B-cell samples. Nineteen percent of the differentially methylated genes were involved in transcriptional regulation. Aberrant hypermethylation was found in all HOX gene clusters and a significant number of WNT signaling pathway genes. Hypomethylation occurred more frequently in the gene body including introns, exons, and 3′-UTRs in CLL. The NFATc1 P2 promoter and first intron was found to be hypomethylated and correlated with upregulation of both NFATc1 RNA and protein expression levels in CLL suggesting that an epigenetic mechanism is involved in the constitutive activation of NFAT activity in CLL cells. This comprehensive DNA methylation analysis will further our understanding of the epigenetic contribution to cellular dysfunction in CLL.

Correlation analysis of clinical parameters with epigenetic modifications in the DUX4 promoter in FSHD

Judit Balog, Peter E. Thijssen, Jessica C. de Greef, Bharati Shah, Baziel G.M. van Engelen, Kyoko Yokomori, Stephen J. Tapscott, Rabi Tawil and Silvère M. van der Maarel
Pages 579 - 584
http://dx.doi.org/10.4161/epi.20001
Abstract | Full Text | PDF

The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and –independent (FSHD2) facioscapulohumeral muscular dystrophy patients. Twenty primary fibroblast (5 control, 10 FSHD1 and 5 FSHD2) and 26 primary myoblast (9 control, 12 FSHD1 and 5 FSHD2) cultures originating from patients with FSHD and controls were analyzed. Histone modification levels were determined by chromatin immunoprecipitation. We examined correlations between the chromatin compaction score (ChCS) defined by the H3K9me3:H3K4me2 ratio and an age corrected clinical severity score (CSS) or muscle pathology score (MPS). Possible relationships were investigated using linear regression analysis and significance was tested by Pearson’s product-moment coefficient.

 

We found a significant difference of the ChCS between controls and patients with FSHD1 and between controls and patients with FSHD2. Tissue specific differences in ChCS were also observed. We also found a near-significant relationship between ChCS and the age corrected CSS in fibroblasts but not in myoblasts. Surprisingly, we found a strong correlation between the MPS of the vastus lateralis and the CSS. Our results confirm the D4Z4 chromatin relaxation previously shown to be associated with FSHD in a small number of samples. A possible relationship between clinical and epigenetic parameters could be established in patient fibroblasts, but not in myoblasts. The strong correlation between the MPS of the vastus lateralis and the CSS suggests that this muscle can be used to study for surrogate markers of overall disease severity.

Human cytomegalovirus infection is sensitive to the host cell DNA methylation state and alters global DNA methylation capacity

Atosa Esteki-Zadeh, Mohsen Karimi, Klas Strååt, Ole Ammerpohl, Manuel Zeitelhofer, Maja Jagodic, Marjan Mehrab-Mohseni, Louise Sjöholm, Afsar Rahbar, Cecilia Söderberg-Nauclér and Tomas J. Ekström
Pages 585 - 593
http://dx.doi.org/10.4161/epi.20075
Abstract | Full Text | PDF

Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus that infects and establishes latency in the majority of the human population and may cause fatal infections in immunocompromised patients. Recent data implies a close interaction between HCMV encoded proteins and cellular epigenetic mechanisms such as histone acetylation and deacetylation. In this study, we investigated the interactions between HCMV infection and the DNA methylation machinery in different host cells using several approaches. We found that colon cancer cell line HCT-116 lacking the DNMT1 and DNMT3b methyltransferases was susceptible to HCMV-AD169 infection, while wild-type cells were non-susceptible. Treatment of wild-type HCT-116 cells with 5-azacytidine rendered them susceptible to infection. Further investigation of HCMV infected MRC-5 fibroblasts demonstrated significant global hypomethylation, a phenomenon that was virus strain-specific and associated with the re-localization of DNMT1 and DNMT3b from the nucleus to the cytoplasm. The cytoplasmic accumulation of DNMT1 was also evident in in vitro infected macrophages and in epithelial cells in tissue samples from patients with inflammatory bowel disease and concomitant HCMV infection. Foscavir treatment of virus infected fibroblasts did not affect the majority of the virus induced nuclear exclusion of DNMT1, which suggest that it is dependent on viral IE gene products. In conclusion, HCMV infection results in profound effects on the host cell DNA methylation machinery and is associated with inflammation in vivo. Our results improve the understanding of cytomegalovirus pathogenesis and open the search for new antiviral therapy targets. These findings may also contribute to the further understanding of mechanisms involved in DNA methylation abnormalities in physiological and pathological conditions.

Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life

Deli Wang, Xin Liu, Ying Zhou, Hehuang Xie, Xiumei Hong, Hui-Ju Tsai, Guoying Wang, Rong Liu and Xiaobin Wang
Pages 594 - 605
http://dx.doi.org/10.4161/epi.20117
Abstract | Full Text | PDF

Prenatal development and early childhood are critical periods for establishing the tissue-specific epigenome, and may have a profound impact on health and disease in later life. However, epigenomic profiles at birth and in early childhood remain largely unexplored. The focus of this report is to examine the individual variation and longitudinal pattern of genome-wide DNA methylation levels from birth through the first two years of life in 105 Black children (59 males and 46 females) enrolled at the Boston Medical Center. We performed epigenomic mapping of cord blood at birth and venous blood samples from the same set of children within the first two years of life using Illumina Infinium Humanmethylation27 BeadChip. We observed a wide range of inter-individual variations in genome-wide methylation at each time point including lower levels at CpG islands, TSS200, 5′UTR and 1st Exon locations, but significantly higher levels in CpG shores, shelves, TSS1500, gene body and 3′UTR. We identified CpG sites with significant intra-individual longitudinal changes in the first two years of life throughout the genome. Specifically, we identified 159 CpG sites in males and 149 CpG sites in females with significant longitudinal changes defined by both statistical significance and magnitude of changes. These significant CpG sites appeared to be located within genes with important biological functions including immunity and inflammation. Further studies are needed to replicate our findings, including analysis by specific cell types, and link those individual variations and longitudinal changes with specific health outcomes in early childhood and later life.

White blood cell global methylation and IL-6 promoter methylation in association with diet and lifestyle risk factors in a cancer-free population

Fang Fang Zhang, Regina M. Santella, Mary Wolff, Maya A. Kappil, Steven B. Markowitz and Alfredo Morabia
Pages 606 - 614
http://dx.doi.org/10.4161/epi.20236
Abstract | Full Text | PDF

Altered levels of global DNA methylation and gene silencing through methylation of promoter regions can impact cancer risk, but little is known about their environmental determinants. We examined the association between lifestyle factors and levels of global genomic methylation and IL-6 promoter methylation in white blood cell DNA of 165 cancer-free subjects, 18–78 years old, enrolled in the COMIR (Commuting Mode and Inflammatory Response) study, New York, 2009–2010. Besides self-administrated questionnaires on diet and physical activity, we measured weight and height, white blood cell (WBC) counts, plasma levels of high sensitivity C-reactive protein (hs-CRP), and genomic (LINE-1) and gene-specific methylation (IL-6) by pyrosequencing in peripheral blood WBC. Mean levels of LINE-1 and IL-6 promoter methylation were 78.2% and 57.1%, respectively. In multivariate linear regression models adjusting for age, gender, race/ethnicity, body mass index, diet, physical activity, WBC counts and CRP, only dietary folate intake from fortified foods was positively associated with LINE-1 methylation. Levels of IL-6 promoter methylation were not significantly correlated with age, gender, race/ethnicity, body mass index, physical activity or diet, including overall dietary patterns and individual food groups and nutrients. There were no apparent associations between levels of methylation and inflammation markers such as WBC counts and hs-CRP. Overall, among several lifestyle factors examined in association with DNA methylation, only dietary folate intake from fortification was associated with LINE-1 methylation. The long-term consequence of folate fortification on DNA methylation needs to be further evaluated in longitudinal settings.

Standardization and quality controls for the methylated DNA immunoprecipitation technique

Sofia Lisanti, Thomas von Zglinicki and John C. Mathers
Pages 615 - 625
http://dx.doi.org/10.4161/epi.20028
Abstract | Full Text | PDF

MeDIP (Methylated DNA Immunoprecipitation) is a relatively recent technique aimed to enrich the methylated fraction of DNA with an antibody directed against 5-methyl-cytosine. MeDIP processed samples are suitable for investigation of the methylation status of specific genomic loci and for performing genome-wide screening when hybridized to DNA methylation microarrays or analyzed by deep sequencing. Here, we describe a standardization protocol and quality controls to assess the specificity, reproducibility and efficiency of the MeDIP procedure. These may have utility when comparing results between samples and experiments within laboratories and between laboratories.

A genomic reservoir for Tnfrsf genes is developmentally regulated and imprinted in the mouse

Elena de la Casa Esperón, Gaëlle Cordier and Nora Engel
Pages 626 - 634
http://dx.doi.org/10.4161/epi.20243
Abstract | Full Text | PDF

Tumor necrosis factor receptor superfamily is composed of at least 26 members in the mouse, three of which exist as a cluster within the imprinted Kcnq1 domain on chromosome 7. Tnfrsf22, 23 and 26 contain typical cystein-rich domains and Tnfrsf22 and 23 can bind ligands but have no signaling capacity. Thus, they are assumed to be decoy receptors. The developmental expression profile of these genes is unknown and knowledge of their imprinting patterns is incomplete and controversial. We found that all three genes are expressed during mouse embryonic development, and that they have a strong maternal bias, indicating that they may be affected by the KvDMR, the Kcnq1 imprinting control region. We found expression of an antisense non-coding RNA, AK155734, in embryos and some neonatal tissues. This RNA overlaps the Tnfrsf22 and possibly the Tnfrsf23 coding regions and is also expressed with a maternal bias. We were interested in exploring the evolutionary origins of the three Tnfrsf genes, because they are absent in the orthologous human Kcnq1 domain. To determine whether the genes were deleted from humans or acquired in the rodent lineage, we performed phylogenetic analyses. Our data suggest that TNFRSF sequences were duplicated and/or degenerated or eliminated from the KCNQ1 region several times during the evolution of mammals. In humans, multiple mutations (point mutations and/or deletions) have accumulated on the ancestral TNFRSF, leaving a single short non-functional sequence.

Open Access Article

DMSO is a strong inducer of DNA hydroxymethylation in pre-osteoblastic MC3T3-E1 cells

Roman Thaler, Silvia Spitzer, Heidrun Karlic, Klaus Klaushofer and Franz Varga
Pages 635 - 651
http://dx.doi.org/10.4161/epi.20163
Abstract | Full Text | PDF

Artificial induction of active DNA demethylation appears to be a possible and useful strategy in molecular biology research and therapy development. Dimethyl sulfoxide (DMSO) was shown to cause phenotypic changes in embryonic stem cells altering the genome-wide DNA methylation profiles. Here we report that DMSO increases global and gene-specific DNA hydroxymethylation levels in pre-osteoblastic MC3T3-E1 cells. After 1 day, DMSO increased the expression of genes involved in DNA hydroxymethylation (TET) and nucleotide excision repair (GADD45) and decreased the expression of genes related to DNA methylation (Dnmt1, Dnmt3b, Hells). Already 12 hours after seeding, before first replication, DMSO increased the expression of the pro-apoptotic gene Fas and of the early osteoblastic factor Dlx5, which proved to be Tet1 dependent. At this time an increase of 5-methyl-cytosine hydroxylation (5-hmC) with a concomitant loss of methyl-cytosines on Fas and Dlx5 promoters as well as an increase in global 5-hmC and loss in global DNA methylation was observed. Time course-staining of nuclei suggested euchromatic localization of DMSO induced 5-hmC. As consequence of induced Fas expression, caspase 3/7 and 8 activities were increased indicating apoptosis. After 5 days, the effect of DMSO on promoter- and global methylation as well as on gene expression of Fas and Dlx5 and on caspases activities was reduced or reversed indicating down-regulation of apoptosis. At this time, up regulation of genes important for matrix synthesis suggests that DMSO via hydroxymethylation of the Fas promoter initially stimulates apoptosis in a subpopulation of the heterogeneous MC3T3-E1 cell line, leaving a cell population of extra-cellular matrix producing osteoblasts. 

Open Access Article

Different measures of “genome-wide” DNA methylation exhibit unique properties in placental and somatic tissues

E. Magda Price, Allison M. Cotton, Maria S. Peñaherrera, Deborah E. McFadden, Michael S. Kobor and Wendy P. Robinson
Pages 652 - 663
http://dx.doi.org/10.4161/epi.20221
Abstract | Full Text | PDF

DNA methylation of CpGs located in two types of repetitive elements—LINE1 (L1) and Alu—is used to assess “global” changes in DNA methylation in studies of human disease and environmental exposure. L1 and Alu contribute close to 30% of all base pairs in the human genome and transposition of repetitive elements is repressed through DNA methylation. Few studies have investigated whether repetitive element DNA methylation is associated with DNA methylation at other genomic regions, or the biological and technical factors that influence potential associations. Here, we assess L1 and Alu DNA methylation by Pyrosequencing of consensus sequences and using subsets of probes included in the Illumina Infinium HumanMethylation27 BeadChip array. We show that evolutionary age and assay method affect the assessment of repetitive element DNA methylation. Additionally, we compare Pyrosequencing results for repetitive elements to average DNA methylation of CpG islands, as assessed by array probes classified into strong, weak and non-islands. We demonstrate that each of these dispersed sequences exhibits different patterns of tissue-specific DNA methylation. Correlation of DNA methylation suggests an association between L1 and weak CpG island DNA methylation in some of the tissues examined. We caution, however, that L1, Alu and CpG island DNA methylation are distinct measures of dispersed DNA methylation and one should not be used in lieu of another. Analysis of DNA methylation data is complex and assays may be influenced by environment and pathology in different or complementary ways.




BOOK REVIEW

Open Access Article

Review of Non-coding RNAs and the epigenetic regulation of gene expression: A book edited by Kevin Morris

Marguerite Blignaut
Pages 664 - 666
http://dx.doi.org/10.4161/epi.20170
Abstract | Full Text | PDF

Advances in sequencing and detection technology over the past two decades, highlighted by the data explosion brought about by the human genome project, have transformed what was previously assumed to be a relatively simple genetic landscape into a new picture where the so-called “dark matter” of the genome has stolen the spotlight from the not so hip protein-coding genes. The simplified central dogma of molecular biology, in which a gene encodes for a protein via a messenger RNA (mRNA), is still at the core of genetics but is now caught in a much more complex web of regulation by the genomic region previously known as “junk” DNA. Books such as Non-coding RNAs and epigenetic regulation of gene expression, published by Caister Academic Press, become essential guidelines to help us understand the current status of the very fast paced field of RNA research, which has only just started to uncover the roles of non-coding RNAs (ncRNAs) in the regulation of gene expression.




ERRATA

Open Access Article

Erratum to: Lepeule J, Baccarelli A, Tarantini L, Motta V, Cantone L, Litonjua AA, et al. Gene promoter methylation is associated with lung function in the elderly: The normative aging study. Epigenetics 2012; 7:261-9.

Johanna Lepeule, Andrea Baccarelli, Letizia Tarantini, Valeria Motta, Laura Cantone, Augusto A. Litonjua, David Sparrow, Pantel S. Vokonas and Joel Schwartz
Page 667
http://dx.doi.org/10.4161/epi.20942
Abstract | Full Text | PDF

It has come to the attention of the authors that Table 5 was not included in Epigenetics Volume 7, Issue 3 in the manuscript: Lepeule J, Baccarelli A, Tarantini L, Motta V, Cantone L, Litonjua AA, et al. Gene promoter methylation is associated with lung function in the elderly: The normative aging study. Epigenetics 2012; 7:261-9.

The citation for Table 5 should have appeared on p. 264, “Sensitivity analyses. The sensitivity analyses including par­ticipants with chronic lung diseases showed similar associations between lung function and DNA methylation as the main analy­ses, with only slight variations in significance (Table 5).”

Open Access Article

Erratum to: Langevin SM, Houseman EA, Christensen BC, Wiencke JK, Nelson HH, Karagas MR, et al. The influence of aging, environmental exposures and local sequence features on the variation of DNA methylation in blood. Epigenetics 2011; 6:908-19.

Scott M. Langevin, E. Andrés Houseman, Brock C. Christensen, John K. Wiencke, Heather H. Nelson, Margaret R. Karagas, Carmen J. Marsit and Karl T. Kelsey
Page 668
http://dx.doi.org/10.4161/epi.20943
Abstract | Full Text | PDF

Authors Scott M. Langevin and E. Andres Houseman contributed equally and should be listed as joint first authors in Epigenetics Volume 6, Issue 7 in the manuscript: Langevin SM, Houseman EA, Christensen BC, Wiencke JK, Nelson HH, Karagas MR, et al. The influence of aging, environmental exposures and local sequence features on the variation of DNA methylation in blood. Epigenetics 2011; 6:908-19.