Genomic Imprinting and Epigenetic Control of Development

Abstract

SUMMARYEpigenetic mechanisms are extensively utilized during mammalian development. Specific patterns of gene expression are established during cell fate decisions, maintained as differentiation progresses, and often augmented as more specialized cell types are required. Much of what is known about these mechanisms comes from the study of two distinct epigenetic phenomena: genomic imprinting and X-chromosome inactivation. In the case of genomic imprinting, alleles are expressed in a parent-of-origin-dependent manner, whereas X-chromosome inactivation in females requires that only one X chromosome is active in each somatic nucleus. As model systems for epigenetic regulation, genomic imprinting and X-chromosome inactivation have identified and elucidated the numerous regulatory mechanisms that function throughout the genome during development.

SNP-guided identification of monoallelic DNA-methylation events from enrichment-based sequencing data

“…Although imprinting is a well-investigated topic and several studies already provided evidence (e.g. compu-tational predictions based on DNA sequence characteristics or detection of monoallelic expression) of some regions with monoallelic DNA-methylation (2,3,(10)(11)(12)(13)(14)(15)(16), only a few imprinted regions are well characterized in humans, like, for example, the IGF2/H19 region. Furthermore, monoallelic methylation has recently been recognized as very common at non-imprinted loci affecting autosomal genes, regulating, for example, the production of specific antibodies and receptors in the immune system as well as the selection of olfactory receptors (17,18).…”

“…The expressed allele can be randomly selected (e.g. Xchromosome inactivation and some autosomal genes) or predetermined by parental imprinting (1)(2)(3). Erroneous monoallelic expression has been associated to several genetic disorders, like the Prader-Willi syndrome, as well as to certain forms of cancer, like Wilms' tumour.…”

microRNA-7 Suppresses the Invasive Potential of Breast Cancer Cells and Sensitizes Cells to DNA Damages by Targeting Histone Methyltransferase SET8

“…Epigenetic regulation, by means of DNA methylation, histone modification, chromatin remodeling, and miRNAs, play important roles in a wide range of biological processes, such as X-chromosome inactivation (32), imprinting (33), reprogramming (34), and gene silencing (35). Each of the epigenetic mechanisms does not work alone but forms an essential and intricate network with each other.…”

Epigenetic alterations in endocrine-related cancer

“…These CpG islands are present in 60% of genes and are usually non-methylated, except in those genes subject to genomic imprinting, X chromosome inactivation, or tissue-specific repression (Antequera 2003). By contrast, those CpG dinucleotides that are scattered throughout the genome are more methylated and located mainly in the bodies of genes, intergenic regions, repetitive sequences, and transposons (MartinSubero 2011, Fedoriw et al 2012. In the context of CpG islands, DNA methylation is sometimes associated with transcriptional repression, this being an important mechanism of gene regulation.…”

“…It has been proposed that, when CpG sites are part of non-coding, repetitive sequences and transposons, the role of methylation is to preserve chromosome stability by preventing the reactivation of mobile elements and maintain the integrity of chromosomes (Bird 2002). Through the maintenance of chromosomal stability and the regulation of gene expression, DNA methylation is crucial for processes such as cell differentiation and embryonic development (Fedoriw et al 2012). It is carried out by a group of enzymes known as DNA cytosine-5-methyltransferases (DNMTs), which transfer the methyl group from S-adenosylmethionine (SAMe) to the C5 position of cytosine.…”