Active Genes on Inactive Sex Chromosomes
Sex chromosome inactivation is precisely regulated by epigenetic mechanisms. Nevertheless, some genes escape the silencing process. In male germ cells, DNA damage response factor RNF8 establishes active epigenetic modifications on the silent sex chromosomes during meiosis, and activates escape genes during a state of sex chromosome-wide silencing in postmeiotic spermatids. Sin and Namekawa describe how epigenetic processes have helped to shape the evolution of sex chromosome-linked genes.
RASSF2 Methylation as a Marker of Ewing Sarcoma
Several members of the Ras-association domain family of genes (RASSF) are frequently methylated in common sporadic cancers. In this issue of Epigenetics, Gharanei et al. investigated the methylation status of RASSF1A and RASSF2 in Ewing sarcoma. Their results suggest that both RASSF1A and RASSF2 are novel epigenetically inactivated tumor suppressor genes in this disease and that RASSF2 methylation may have prognostic implications for Ewing sarcoma patients.
DNA Demethylation and Zebrafish Fin Regeneration
Dedifferentiation is a critical step during regeneration in amphibians and fish. Now, Hirose et al. show that dedifferentiated cells show reduced levels of 5mC and 5hmC, independent of cell proliferation, by 24 hours post amputation. Their findings suggest that the transient reduction of 5mC and 5hmC in dedifferentiated cells is associated with active demethylation during regeneration of zebrafish fin.
Human Prostate Cancer and HDACis
Histone deacetylases (HDACs) are important targets for cancer treatment and HDAC-inhibitors (HDACis) have been approved for the treatment of patients with cutaneous T-cell lymphoma. In this issue, Kortenhorst et al. studied combination strategies with HDACis in order to improve the clinical benefit of HDACis in solid tumors.The authors generated a comprehensive list of genes and pathways affected upon HDACi-treatment in prostate cancer cells, identifying biological processes that are potential treatment targets for combination therapy.
DNA Methylation in Colorectal Cancer
Naumov et al. used Illumina’s Infinium HumanMethylation450 BeadChip arrays to examine genome-wide DNA methylation profiles in colorectal cancer. The authors show that the methylation profiles of tumors and healthy tissue samples can be clearly distinguished from one another and that the main source of methylation variability is associated with disease status.
Epigenetics of Gestational Diabetes Mellitus
Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk for chronic diseases. Ruchat et al. investigated if GDM exposure impacts the offspring’s methylome and used an epigenomic approach to explore this hypothesis. Their results suggest that GDM has epigenetic effects on genes preferentially involved in the metabolic diseases pathway, with consequences on fetal growth and development, providing supportive evidence that DNA methylation is involved in fetal metabolic programming.
Reduced Fetal Growth, DNMT1 and eNOS Expression
Reduced fetal growth is associated with endothelial dysfunction and cardiovascular risk in offspring. The nitric oxide (NO) system has been implicated in these effects. In this issue, Krause et al. show that expression of eNOS (a key gene in the NO system) in endothelial cells derived from intrauterine growth restricted fetuses is programmed by altered DNA methylation and can be reversed by transient silencing of the DNA methylation machinery.
Virus-Host Methylome Analysis in HNSCC
Wilson et al. conducted whole-genome DNA methylation analysis in order to better understand the dynamics of HPV integration and its effect on both viral and host methylomes. The authors identified differentially methylated regions (DMRs) in HPV+ head and neck squamous cell carcinoma (HNSCC). These DMRs revealed new targets for HPV-mediated methylation changes at regions not covered by array-based platforms, including the recently identified super-enhancers.
Global DNA Methylation and Aflatoxin B1 Exposure
Global DNA hypomethylation and aflatoxin B1 (AFB1) exposure are associated with increased hepatocellular carcinoma risk. Wu et al. assessed the relationship between AFB1 exposure and global DNA methylation, which may have implications for the epigenetic effect of AFB1 on hepatocellular carcinoma development. Their results suggest that changes in DNA methylation may represent an epigenetic biomarker of dietary AFB1 exposure.
Histone Signature of Metanephric Mesenchyme Cell Lines
The metanephric mesenchyme (MM) gives rise to nephrons, the filtering units of the mature kidney and is composed of uninduced and induced cells. Now, McLaughlin et al. used two mouse clonal cell lines to study the chromatin signature of uninduced and induced cells, and found that it correlates strongly with their gene expression states, suggesting a role of chromatin-based mechanisms in MM cell fate.
Zebrafish Brain Methylome
In this issue of Epigenetics, Chatterjee et al. evaluated the technique of reduced representation bisulfite sequencing (RRBS) in zebrafish by generating four single-nucleotide resolution DNA methylomes of the adult brain. This analysis provides a roadmap for generating reproducible base-pair level methylomes for zebrafish using RRBS and show that RRBS is a suitable technique for global methylation analysis in zebrafish.
H19 Methylation in Infertile Males
Aberrant methylation at the H19 paternal imprinted gene has been identified in different cohorts of infertile males. Rotondo et al.investigated the methylation status of the H19 gene in semen DNA samples from infertile males affected by MTHFR gene promoter hypermethylation. Their results underscore the association between H19 methylation defects and hypermethylation of the MTHFR gene promoter in normal semen samples and suggest that aberrant methylation at H19 may occur in the normal sperm of infertile males affected by MTHFR gene dysfunction.
Meeting Report
The First German-Catalan Workshop on Epigenetics and Cancer was held in Heidelberg, Germany (June 17–19, 2013), where cutting-edge laboratories discussed the latest breakthroughs in the field. A summary of the highlights of this workshop is presented in this issue.