1. Bivalent Regions of Cytosine Methylation and H3K27 Acetylation Suggest an Active Role for DNA Methylation at Enhancers.

    Molecular Cell 62(3):422 (2016) PMID 27153539 PMCID PMC4859934

    The role of cytosine methylation in the structure and function of enhancers is not well understood. In this study, we investigate the role of DNA methylation at enhancers by comparing the epigenomes of the HCT116 cell line and its highly demethylated derivative, DKO1. Unlike promoters, a portion...
  2. Identification of DNA Methylation-Independent Epigenetic Events Underlying Clear Cell Renal Cell Carcinoma.

    Cancer Research 76(7):1954 (2016) PMID 26759245 PMCID PMC4873378

    Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneo...
  3. DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells.

    Nature Communications 7:11453 (2016) PMID 27121154 PMCID PMC4853477

    Promoter DNA methylation is a key epigenetic mechanism for stable gene silencing, but is correlated with expression when located in gene bodies. Maintenance and de novo DNA methylation by catalytically active DNA methyltransferases (DNMT1 and DNMT3A/B) require accessory proteins such as UHRF1 an...
  4. DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts.

    Cell 162(5):961 (2015) PMID 26317465 PMCID PMC4843502

    DNA-demethylating agents have shown clinical anti-tumor efficacy via an unknown mechanism of action. Using a combination of experimental and bioinformatics analyses in colorectal cancer cells, we demonstrate that low-dose 5-AZA-CdR targets colorectal cancer-initiating cells (CICs) by inducing vi...
  5. The role of DNA methylation in directing the functional organization of the cancer epigenome.

    Genome Research 25(4):467 (2015) PMID 25747664 PMCID PMC4381519

    The holistic role of DNA methylation in the organization of the cancer epigenome is not well understood. Here we perform a comprehensive, high-resolution analysis of chromatin structure to compare the landscapes of HCT116 colon cancer cells and a DNA methylation-deficient derivative. The NOMe-se...
  6. Genome-wide nucleosome occupancy and DNA methylation profiling of four human cell lines.

    Genomics Data 3:94 (2015) PMID 26484155 PMCID PMC4535833

    DNA methylation and nucleosome positioning are two key mechanisms that contribute to the epigenetic control of gene expression. During carcinogenesis, the expression of many genes is altered alongside extensive changes in the epigenome, with repressed genes often being associated with local DNA ...
  7. Gene body methylation can alter gene expression and is a therapeutic target in cancer.

    Cancer Cell 26(4):577 (2014) PMID 25263941 PMCID PMC4224113

    DNA methylation in promoters is well known to silence genes and is the presumed therapeutic target of methylation inhibitors. Gene body methylation is positively correlated with expression, yet its function is unknown. We show that 5-aza-2'-deoxycytidine treatment not only reactivates genes but ...
  8. Reconfiguration of nucleosome-depleted regions at distal regulatory elements accompanies DNA methylation of enhancers and insulators in cancer.

    Genome Research 24(9):1421 (2014) PMID 24916973 PMCID PMC4158760

    It is well established that cancer-associated epigenetic repression occurs concomitant with CpG island hypermethylation and loss of nucleosomes at promoters, but the role of nucleosome occupancy and epigenetic reprogramming at distal regulatory elements in cancer is still poorly understood. Here...
  9. Reprogramming of the human intestinal epigenome by surgical tissue transposition.

    Genome Research 24(4):545 (2014) PMID 24515120 PMCID PMC3975055

    Extracellular cues play critical roles in the establishment of the epigenome during development and may also contribute to epigenetic perturbations found in disease states. The direct role of the local tissue environment on the post-development human epigenome, however, remains unclear due to li...
  10. A panel of three markers hyper- and hypomethylated in urine sediments accurately predicts bladder cancer recurrence.

    Clinical Cancer Research 20(7):1978 (2014) PMID 24691641

    The high risk of recurrence after transurethral resection of bladder tumor of nonmuscle invasive disease requires lifelong treatment and surveillance. Changes in DNA methylation are chemically stable, occur early during tumorigenesis, and can be quantified in bladder tumors and in cells shed int...
  11. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome.

    Genome Research 24(3):454 (2014) PMID 24299735 PMCID PMC3941110

    Epigenetic information is available from contemporary organisms, but is difficult to track back in evolutionary time. Here, we show that genome-wide epigenetic information can be gathered directly from next-generation sequence reads of DNA isolated from ancient remains. Using the genome sequence...
  12. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers.

    Oncotarget 5(3):587 (2014) PMID 24583822 PMCID PMC3996658

    Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacit...
  13. Establishment of active chromatin structure at enhancer elements by mixed-lineage leukemia 1 to initiate estrogen-dependent gene expression.

    Nucleic Acids Research 42(4):2245 (2014) PMID 24288367 PMCID PMC3936730

    A number of genome-wide analyses have revealed that estrogen receptor α binding to and regulation of its target genes correlate with binding of FOXA1, a pioneer factor, to nearby DNA sites in MCF-7 breast cancer cells. The enhancer element-specific histone H3K4me1/2 mark is enriched at the speci...
  14. At the tipping point for epigenetic therapies in cancer.

    Journal of Clinical Investigation 124(1):14 (2014) PMID 24382384 PMCID PMC3871262

    The field of epigenetics has exploded in the last two decades, with incredible advances in recent years driven by high-throughput sequencing studies. Cancer cells frequently exhibit marked changes in DNA methylation and histone modification during tumorigenesis and tumor progression. These chang...
  15. Alterations of immune response of Non-Small Cell Lung Cancer with Azacytidine.

    Oncotarget 4(11):2067 (2013) PMID 24162015 PMCID PMC3875770

    Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines ...
  16. Alterations in deoxyribonucleic acid (DNA) methylation patterns of Calca, Timp3, Mmp2, and Igf2r are associated with chronic cystitis in a cyclophosphamide-induced mouse model.

    Urology 82(1):253.e9 (2013) PMID 23806407 PMCID PMC3697025

    To determine whether epigenetic changes occur during cyclophosphamide-induced chronic bladder inflammation in mice. Epigenetic changes play a role in the regulation of inflammatory genes in noncancer diseases such as asthma and chronic obstructive pulmonary disease. However, epigenetic (deoxyrib...
  17. How long will I be blue? Prolonged skin staining following sentinel lymph node biopsy using intradermal patent blue dye.

    Breast Care 8(3):199 (2013) PMID 24415970 PMCID PMC3728719

    Blue dye used for sentinel lymph node biopsy (SLNB) in breast cancer patients may cause prolonged skin discoloration at the site of injection. The aim of this study was to assess the duration of such skin discoloration. 236 consecutive patients who had undergone breast conserving surgery and SLN...
  18. Functional DNA demethylation is accompanied by chromatin accessibility.

    Nucleic Acids Research 41(7):3973 (2013) PMID 23408854 PMCID PMC3627572

    DNA methylation inhibitors such as 5-aza-2'-deoxycytidine (5-Aza-CdR) are currently used for the treatment of myelodysplastic syndrome. Although global DNA demethylation has been observed after treatment, it is unclear to what extent demethylation induces changes in nucleosome occupancy, a key d...
  19. SNF5 is an essential executor of epigenetic regulation during differentiation.

    PLoS Genetics 9(4):e1003459 (2013) PMID 23637628 PMCID PMC3636213

    Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory regions and serves an instructive role for gene expression. Chromatin remodelers, such as the BAF complexes, are responsible for establishing nucleosome occupancy patterns, which are key to epigeneti...
  20. Diagnostic markers of urothelial cancer based on DNA methylation analysis.

    BMC Cancer 13:275 (2013) PMID 23735005 PMCID PMC3691617

    Early detection and risk assessment are crucial for treating urothelial cancer (UC), which is characterized by a high recurrence rate, and necessitates frequent and invasive monitoring. We aimed to establish diagnostic markers for UC based on DNA methylation. In this multi-center study, three in...