In this issue of Epigenetics

Protecting DNA Methylation at Imprinted Genes; pp. 969-75

During the transition from oocyte to embryo and early pre-implantation development, nuclear reprogramming occurs. This is the time when the epigenome is reset in the maternal and paternal pronuclei to a ground state, a step that is essential to ensure the totipotency of the zygote. Nevertheless, a subset of methylated sequences (imprinted loci) must retain their differential methylation status, acquired during gametogenesis, throughout embryogenesis and in adult tissues. In this issue of Epigenetics, Messerschmidt discusses how imprinting marks are protected/maintained during reprogramming in pre-implantation embryos. Specifically, he reviews the role of an epigenetic modifier complex formed by ZFP57 and TRIM28/KAP1 and the way in which this complex interacts with other players and with embryonic chromatin and imprinted genes.

H3K27me3 Remodeling during Early Development; pp. 976-81

During fertilization, dynamic changes in chromatin allow the transition from the chromatin configuration found in the oocyte and the sperm into an embryonic pluripotent structure. Specifically, H3K27me3 is a repressive epigenetic mark that changes dynamically during pre-implantation development. In this issue of Epigenetics, Bogliotti and Ross discuss the potential mechanisms behind H3K27me3 remodeling during early mammalian development. The authors postulate that the repressive H3K27me3 mark is globally erased from the parental genomes in order to remove the gametic epigenetic program and to establish a pluripotent embryonic epigenome.

An Overview of Epigenetic Biomedical Resources; pp. 982-6

The generation of enormous amounts of data has driven the need for more advanced storage solutions and shared access through a range of public repositories. The number of such biomedical resources is increasing constantly and mining these large and diverse data sets continues to present real challenges. Shakya et al. present an invaluable general overview of currently available biomedical resources, together with remarks on their data mining and analysis capabilities. The authors provide a guideline for the assessment and comparison of currently available resources, concentrating particularly in those related to epigenetics/epigenomics.

Epigenetics and Fibrotic Disease; pp. 987-93

Fibrosis consists on an excessive extracellular matrix accumulation that ultimately destroys tissue architecture and eventually abolishes normal organ function. No antifibrotic therapies have been described that can reverse, stop or delay the formation of scar tissue in most fibrotic organs. A recent hypothesis suggests that the cells involved in this process gain an altered heritable phenotype that promotes excessive fibrotic tissue accumulation. Robinson et al. now review the most recent observations that suggest that there is a link between epigenetic modifications and fibrotic disease, discussing the roles of DNA methylation and histone modifications.

Regulating DNMT1 Stability and Function; pp. 994-1007

Kar et al. review the various regulatory mechanisms and interactions of DNMT1, the maintenance methyltransferase. The authors provide a useful overview of DNMT1 targeting and function, contributing to the understanding of the mechanisms by which DNA methylation participates in critical developmental and physiological processes.

CpG DNA Methylation and Cognition; pp. 1008-19

Cognitive abilities, particularly memory formation, vary substantially in the elderly. The range of cognitive outcomes could be modulated by epigenetic modifications that occur in response to environmental influences and affect gene transcription in cognitively relevant brain regions. To investigate the influence of epigenetics on specific gene expression profiles in specific regions of the brain, Haberman et al. examined genomic CpG DNA methylation in the promoter regions of three neurophysiologically relevant genes (Gabra5, Hspa5 and Syn1) whose expression levels decrease with age and correlate with spatial memory performance. Their data suggest that methylation at single CpGs may have a role in determining individual cognitive differences.

Global DNA Methylation in Postmenopausal Women; pp. 1020-8

In this issue of Epigenetics, Ulrich et al. investigated associations between DNA methylation and dietary factors, sex-steroid hormones, and metabolic, lipid, inflammation, immune and one-carbon biomarkers. The authors studied 173 overweight/obese postmenopausal women and analyzed global DNA methylation in lymphocytes using the pyrosequencing assay for LINE-1 repeats. In analyses stratified by folate status, DNA methylation was negatively associated with sex hormone concentrations among women with low serum folate levels. Conversely, among women with high serum folate levels, DNA methylation was positively associated with several immune markers. The results from this screening suggest that global DNA methylation is differentially associated with sex hormones and immune markers depending on one-carbon status.

Oocyte-specific Linker Histone H1foo; pp. 1029-36

Linker histone H1foo is a distinct member of the H1 histone family that is present in mammalian oocytes and is essential for oocyte maturation in mice. Hayakawa et al. studied the function of H1foo in embryonic stem cells that ectopically express H1foo fused to an EGFP (H1foo-EGFP). Ectopic expression of H1foo prevented normal differentiation into embryoid bodies. In addition, H1foo-EGFP bound selectively to a set of hypomethylated genomic loci, wich were decondensed by H1foo binding.

Specific KLKs as Biomarkers for Prostate Cancer; pp. 1037-45

Human kallikrein-related peptidases (KLKs) have emerged as an important family of cancer biomarkers. Now, Olkhov-Mitsel et al. have studied the epigenetic regulation of KLKs and its implication in prostate cancer. The authors have assessed the biological effect of DNA methylation on KLK6 and KLK10 expression and observed increased expression on both KLKs after inducing demethylation. Studies with prostate cancer patients suggest that KLK6 and KLK10 DNA methylation distinguishes organ confined from locally invasive prostate cancer and may have prognostic value.

Dnmt3b mRNA in Mouse Liver; pp. 1046-56

DNA methyltransferase 3B (Dnmt3b) is involved in de novo DNA methylation and genomic stability. In adult mouse liver, Dnmt3b mRNA expression shows diurnal variation. Maekawa et al. now studied the mechanism underlying this diurnal expression pattern. The authors showed that the expression pattern of Dnmt3b closely coincided with that of Bmal1, which encodes a core clockwork protein. Also, since the diurnal pattern of Dnmt3b mRNA expression coincided with weaning and scheduled feeding, the authors separated the feeding cycle from the light/dark cycle and observed a phase-shift in the expression, suggesting that feeding plays a critical role as an entrainment signal. In addition, Bmal1 deficiency resulted in significantly higher levels of Dnmt3b. These results suggest that the feeding and hepatic clockwork generated by the clock genes, including Bmal1, regulate the diurnal variation in Dnmt3b mRNA expression and the consequent dynamic changes in global DNA methylation.

H4K12ac in Human Sperm; pp.1057-70

In sperm chromatin, protamines are the predominant nuclear proteins and histones are highly acetylated. H4K12ac is localized in the post-acrosomal region, while protamine-1 is present within the whole nucleus. H4K12ac has been shown to be enriched at CTCF binding sites and at the promoters of genes involved in developmental processes. In this issue of Epigenetics, Paradowska et al. demonstrate that H4K12ac is enriched predominantly between two kilobases from the transcription start site. In addition, the authors identified high expression levels of developmentally relevant transcripts from H4K12ac-associated genes in mature sperm. Aberrant histone acetylation within developmentally important gene promoters in infertile men may reflect insufficient sperm chromatin compaction, which may result in inappropriate transfer of epigenetic information to the oocyte.

Transgenerational Maintenance of Cytosine Methylation; pp. 1071-8

In plants, RNA-directed DNA methylation (RdDM) leads to the methylation of cytosines in all sequence contexts (CG, CHG and CHH) and can target both transgene promoter and coding region. Upon segregation of the RdDM trigger, at least CG methylation can be maintained at promoter regions in the progeny. It is not clear whether coding region methylation can be also maintained. Dalakouras et al. have now showed that the body of a potato spindle tuber viroid (PSTVd) transgene constructs became densely de novo methylated at CG, CHG and CHH sites upon PSTVd infection. The authors observed that in viroid-free progeny plants, asymmetric CHH and CHG methylation was completely lost. However, symmetric CG methylation was stably maintained for at least two generations. The presence of transgene body methylation did not lead to an increase of dimethylation of H3K9 or a decrease of acetylation of H3. These data supports the view that CG methylation can be maintained not only in promoters but also in the body of transgenes and suggest that maintenance of methylation may occur independently of tested chromatin modifications.

Novel Imprinted Genes in Placenta; pp. 1079-90

To date, 150 imprinted genes have been characterized in human and mice, but many more are likely to exist. Starting from human placental material and using a high-throughput strategy, Barbaux et al. identified seven new genes presenting monoallelic expression (ZFAT, ZFAT-AS1, GLIS3, NTM, MAGI2, ZC3H12C and LIN28B). Remarkably, these genes are not imprinted in the mouse placenta, except for Magi2.