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Epigenetic regulation is the mechanism by which gene function is selectively activated or inactivated in the cells. It provides higher-ordered and more specified genetic information, compared with the whole genome itself. Recently, a variety of regulatory proteins including DNA methyltransferases, methyl-CpG binding proteins, histone-modifying enzymes, chromatin remodeling factors, and their multimolecular...
The extra sex combs (esc) gene of Drosophila and its mammalian homologue embryonic ectoderm development (eed) play pivotal roles in establishing Polycomb-group (Pc-G) mediated transcriptional silencing of regulatory genes during early development. We have carried out a two-hybrid screen in yeast to identify maternally expressed proteins that interact directly with the product of the Xenopus eed homologue,...
Multicellular development is programmed by regulated interactions between transcription factors and target genes. Target genes function as nucleosomal arrays whose higher order structure, composition and accessibility to transcription machinery are strictly and dynamically controlled. Several classes of chromatin-associated proteins generate or remove localized, covalent chromatin modifications that...
An organism ultimately reflects the coordinate expression of its genome. The misexpression of a gene can have catastrophic consequences for an organism, yet the mechanics of transcription is a local phenomenon within the cell nucleus. Chromosomal and nuclear position often dictate the activity of a specific gene. Transcription occurs in territories and in discrete localized foci within these territories...
The Additional sex combs (Asx) gene of Drosophila is required to maintain homeotic gene activation and silencing. Here we characterize the three murine homologs of Asx: Additional sex combs-like (Asxl1, Asxl2, and Asxl3) and identify conserved sequence features. The predicted amino acid sequence of Asxl1 has 16% identity and 40% similarity to Drosophila Asx, and 74% identity and 81% similarity to...
Several aspects of epigenetics are strongly linked to non-coding RNAs, especially small RNAs that can direct the cytosine methylation and histone modifications that are implicated in gene expression regulation in complex organisms. A fundamental characteristic of epigenetics is that the same genome can show alternative phenotypes, which are based in different epigenetic states. Some of the most studied...
We evaluated the epigenetic contributions of repetitive DNA elements to human gene regulation. Human proximal promoter sequences show distinct distributions of transposable elements (TEs) and simple sequence repeats (SSRs). TEs are enriched distal from transcriptional start sites (TSSs) and their frequency decreases closer to TSSs, being largely absent from the core promoter region. SSRs, on the other...
Rac2 is a Rho family GTPase that is widely expressed in hematopoietic cells and plays a critical role in host defense. This study investigates the mechanisms responsible for increased Rac2 gene expression during myeloid cell differentiation. Treatment of K562 chronic myelogenous leukemia cells with phorbol-12-myristate-13-acetate (PMA) induces megakaryocytic differentiation and Rac2 gene transcription...
Histone methylation plays an important role in regulating chromatin-mediated gene control and epigenetic-based memory systems that direct cell fate. Enzymes termed histone demethylases directly remove the methyl marks from histones, thus contributing to a dynamically regulated histone methylated genome; however, the biological functions of these newly identified enzymes remain unclear. The JMJD2A-D...
Eukaryotic chromosomal DNA coils around histones to form nucleosomes. Although histone affinity for DNA depends on DNA sequence patterns, how nucleosome positioning is determined by them remains unknown. Here, we show relationships between nucleosome positioning and two structural characteristics of DNA conferred by DNA sequence. Analysis of bendability and hydroxyl radical cleavage intensity of nucleosomal...
The Fragile X mental retardation (FMR1) gene contains a polymorphic CGG trinucleotide repeat in the 5′-untranslated region. The repeat length in the normal population is between 5 and 54 repeats. A repeat length between 55 and 200 is defined as the pre-mutation repeat size. Elderly carriers of the pre-mutation can develop the progressive neurodegenerative disease Fragile X-associated tremor/ataxia...
Several gene databases, including heavily used ones such as the National Center for Biotechnology Information (NCBI) database, erroneously assign, on occasion, literature references to genes or proteins. These mistakes are mostly due to an overlap in gene aliases, whereby two distinct genes share a pseudonym. This is particularly confusing when the gene products have also biological properties in...
To determine if ethanol consumption and alcoholism cause global DNA methylation disturbances, we examined alcoholics and controls using methylation specific microarrays to detect all annotated gene and non-coding microRNA promoters and their CpG islands. DNA was isolated and immunoprecipitated from the frontal cortex of 10 alcoholics and 10 age and gender-matched controls then labeled prior to co-hybridization...
Genome-wide methylation studies frequently lack adequate controls to estimate proportions of background reads in the resulting datasets. To generate appropriate control pools, we developed technique termed nMETR (non-methylated tag recovery) based on digestion of genomic DNA with methylation-sensitive restriction enzyme, ligation of adapter oligonucleotide and PCR amplification of non-methylated sites...
Many exogenous (e.g., toxins, chemicals, ultraviolet, cigarette smoke) and endogenous (e.g., hyperglycemia, dyslipidemia, cytokines, chemokines) agents disrupt the intracellular environment and result in a massive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The molecular damage that ROS/RNS induce is referred to as nitrooxidative stress. The cellular consequences...
Fertilised eggs of Senegalese sole were incubated at 15, 18 or 21°C, and after hatching all larvae were reared at 21°C until 30days post-hatch. By this point larvae from the 18 or 21°C temperature groups had 11 and 9% more muscle fibres than those from 15°C, respectively. Hyperplastic growth during metamorphosis was higher in larvae from 18°C. Embryonic temperature induced gene expression changes,...
Photoperiod manipulation during early juvenile stages can influence growth in Atlantic cod. In the present study, one group of cod juveniles were reared under natural photoperiod conditions for Bodø (67° N, 14° E), whereas their counterparts were kept under continuous illumination. The mean weight of juvenile cod reared under continuous illumination was found to be 13% greater than those kept under...
Jumonji (Jmj) proteins are histone demethylases, which control the identity of stem cells. Jmj genes were characterized from plants to mammals where they have been implicated in the epigenetic regulation of development. Despite the Pacific oyster Crassostrea gigas representing one of the most important aquaculture resources worldwide, the molecular mechanisms governing the embryogenesis and reproduction...
Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including...
The combination of the obesity epidemic and an aging population presents growing challenges for the healthcare system. Obesity and aging are major risk factors for a diverse number of diseases and it is of importance to understand their interaction and the underlying molecular mechanisms. Herein the authors examined the methylation levels of 27578 CpG sites in 46 samples from adult peripheral blood...
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