Translational research : the journal of laboratory and clinical medicine
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Mammalian messenger RNA (mRNA) and long noncoding RNA (lncRNA) contain tens of thousands of posttranscriptional chemical modifications. Among these, the N(6)-methyl-adenosine (m(6)A) modification is the most abundant and can be removed by specific mammalian enzymes. m(6)A modification is recognized by families of RNA binding proteins that affect many aspects of mRNA function. mRNA/lncRNA modification represents another layer of epigenetic regulation of gene expression, analogous to DNA methylation and histone modification.
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The study of epigenetics is intimately linked and inseparable from developmental biology. Many of the genes that imprint epigenetic information on chromatin function during the specification of cell lineages in the developing embryo. These include the histone methyltransferases and their cofactors of the Polycomb and Trithorax gene families. ⋯ In adult tissues, histone methylation marks must be maintained for normal gene expression patterns. In chronic and acute renal disease, epigenetic marks are being characterized and correlated with the establishment of metabolic memory, in part to explain the persistence of pathologies even when optimal treatment modalities are used. Thus, the state of the epigenome in adult cells must be considered when attempting to alleviate or alter gene expression patterns in disease.
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Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Recent work by our and other groups has identified strong genetic predisposition factors for the development of pulmonary fibrosis, and cigarette smoke remains the most strongly associated environmental exposure risk factor. ⋯ Moreover, epigenetic marks represent a promising therapeutic target for IPF. In this review, the disease is introduced, genetic and gene expression studies in IPF are summarized, exposures relevant to IPF and known epigenetic changes associated with cigarette smoke exposure are discussed, and epigenetic studies conducted so far in IPF are summarized. Limitations, challenges, and future opportunities in this field are also discussed.
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Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development or maintenance of persistent pain and possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain.
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The nucleosome remodeling and deacetylase (NuRD) complex is one of the major chromatin remodeling complexes found in cells. It plays an important role in regulating gene transcription, genome integrity, and cell cycle progression. ⋯ Recent genetic and biochemical studies have elucidated the mechanisms of NuRD action in modifying the chromatin landscape. These advances have the potential to lead to new therapeutic approaches to birth defects and cancer.