Centromeric Chromatin pp. 3–13
The centromere is the chromosomal region where the kinetochore assembles, recognizes and attaches to microtubules, so that each sister chromatid can segregate to each daughter cell during cell division. The chromatin structure found at the centromere is the result of highly regulated epigenetic events. González-Barrios et al. describe an integrative model for the epigenetic processes that take place during the recruitment of kinetochore proteins. If alterations of these chromatin regions occur, chromosomal instability is promoted, although segregation may still take place.
DNA Replication, RNAi and Epigenetic Inheritance pp. 14–9
How are conserved epigenetic marks faithfully inherited from one generation to the next? In an attempt to elucidate this question, Gonzalez and Li review the role that DNA polymerase components may play in the inheritance of histone methylation in fission yeast by coordinating DNA replication, RNAi and histone methylation, and explain previously observed cell cycle-regulated RNAi-dependent heterochromatin silencing. The authors propose a model in which, at DNA replication forks, DNA polymerase subunits mediate the recruitment of epigenetic factors required for RNAi and histone modification to heterochromatin to promote the faithful transmission of histone methylation.
Epigenetic Psychopharmacology pp. 20–8
Epigenetic regulation of brain functions plays an important role in the etiology of psychiatric disorders. Boks et al. review how currently used psychiatric drugs influence the brain epigenome and the potential for new epigenetic drugs in the treatment of psychiatric disorders.
RdDM Pathway in Arabidopsis pp. 29–33
Cytosine DNA methylation is an epigenetic mark frequently associated with the silencing of genes and transposons. In Arabidopsis, the establishment of cytosine DNA methylation is performed by DRM2, which is guided to target sequences by siRNAs in a pathway termed RNA-directed DNA methylation (RdDM). Ausin et al. performed a screen for mutants that affect the establishment of DNA methylation by investigating genes that contain predicted RNA-interacting domains.
Microenvironment Control of Cancer Progression pp. 34–46
The role of the microenvironment in human cancer progression is well established. However, the mechanisms by which the tumor microenvironment epigenetically controls genes that are critical to cancer progression remains unclear. DesRochers et al. studied how the microenvironment controls E-cadherin expression by transient epigenetic regulation of its promoter, contributing to the unstable and reversible expression of E-cadherin seen during tumor progression. The authors suggest that epigenetic regulation is a mechanism through which tumor cell colonization of metastatic sites occurs as E-cadherin-expressing cells arise from E-cadherin-deficient cells.
Epigenetic Somatic Mosaicism in Twins pp. 47–54
A study by Galetzka et al. describes monozygotic twins discordant for childhood leukemia and secondary thyroid carcinoma. The authors compare the constitutive promoter methylation of BRCA1 and several other tumor suppressor genes in primary fibroblasts. This monozygotic twin pair represents an impressive example of epigenetic somatic mosaicism, suggesting a role for constitutive epimutations, maybe along with de novo genetic alterations in recurrent tumor development.
Chromatin Dynamics During Cellular Differentiation pp. 55–62
The study of chromatin dynamics across cellular differentiation states could help in the understanding of global gene expression regulation patterns. However, the dynamics of histone marks from a loci-specific perspective during cellular differentiation has not been well studied. Tian et al. describe a method to systematically assess the histone modification variations of genes across various cellular differentiation states. The authors calculated the histone modification variation scores of H3K4me3, H3K27me3 and H3K36me3 for over 1300 curated transcription factors during human blood cell differentiation. Their results suggest that local chromatin state dynamics of transcription factors across cellular differentiation states could imply cell lineage-specific functions.
Aging and Epigenetics pp. 63–70
Because DNA methylation has been associated with age-related diseases, the study of intra-individual changes in gene-specific DNA methylation over time is of utmost importance. Madrigano et al. have estimated the change in DNA methylation due to aging for nine genes in an elderly, community-dwelling cohort of men. Their findings suggest that DNA methylation may reflect differential biological aging.
DNMT3B in Early Neurogenesis pp. 71–82
DNMT3B functions in establishing DNA methylation patterns during development. Missense mutations in DNMT3B cause immunodeficiency, centromere instability and facial anomalies (ICF) syndrome. Martins-Taylor et al. studied the role of DNMT3B in early neurogenesis. DNMT3B appear to mediate large-scale methylation patterns in hESCs; its deficiency in the cells alters the timing of their neuronal differentiation and maturation.
Epigenetics of the Bones pp. 83–91
Osteoblasts are specialized cells that form new bone and also indirectly influence bone resorption by producing factors that modulate osteoclast differentiation. Delgado-Calle et al. studied the role of CpG methylation in the regulation of gene expression in the human bone. Specifically, the authors investigated two osteoblast-derived critical factors: the receptor activator of nuclear factor NF-kB ligand (RANKL) and its soluble decoy receptor osteoprotegerin (OPG). Their results suggest that methylation-dependent mechanisms influence the transcription of these genes, which have critical roles in osteoclastogenesis.
Analyzing LINE1 DNA Methylation pp. 92–105
Changes in DNA methylation have been reported to be an early and fundamental event in the pathogenesis of many human diseases, including cancer. Therefore, high throughput studies to identify and analyze the mode of action of modulators of DNA methylation are critical for the understanding and treatment of these diseases. Newman et al. present the first high resolution melt (HRM) assay to quantitatively analyze differences in murine DNA methylation levels utilizing CpG methylation of LINE1. This assay provides a high throughput, inexpensive and sensitive screening tool for identifying and characterizing DNA methylation changes to LINE1 elements at multiple regions across the genome.
MeDIP: A Comparison of Commercial Kits pp. 106–12
The methylated DNA immunoprecipitation microarray (MeDIP-ChIP) is a genome-wide, high-resolution approach that detects DNA methylation with oligonucleotide tiling arrays or high throughput sequencing platforms. A simplified high-throughput MeDIP assay will enable translational research studies in clinics and populations, which will greatly enhance our understanding of the human methylome. Brebi-Mieville et al. have compared three commercial kits for one of these MeDIP in order to identify which one has better reliability and sensitivity for genomic DNA enrichment.
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