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promoters are embedded in a CpG island that is mostly methylation-free and therefore can be targeted for methylation. Recent human and rodent studies have shown tissue and disease specific expression of untranslated first exons, due in part to changes in GR
Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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et al . 2009 ). The best characterised of these modifications is the C5-methylation of cytosine in CpG dinucleotide motifs. Methylation of CpGs (meCpG) at gene promoters results in transcriptional repression either by interfering with transcription
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. DNA methylation, histone modification patterns, or miRNAscan be potential mechanisms by which lifelong changes in gene expression are maintained. Sexual dimorphism of liver genes may underlie sex differences in hepatic disease, and furthermore, loss
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Instituto de Investigaciones Biomédicas, Centro Nacional de Biotecnología, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Arturo Duperier 4, 28029 Madrid, Spain
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was DNA methylation in the 1970s ( Holliday & Pugh 1975 ). However, epigenetics also addresses covalent modifications of histones and the mechanisms through which they alter chromatin structure ( Turner 1998 ). Other gene regulation mechanisms such as
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Department of Clinical Medicine, Endocrinology and Diabetes, Aarhus University Hospital, Aarhus, Denmark
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a presentation and discussion of the windows of susceptibility for epigenetic inheritance through the male germ line. While the review focuses on DNA methylation, we also acknowledge the importance of non-coding RNA (ncRNA) (i.e. microRNA (miRNA
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et al. 2014 , Oh et al. 2014 , 2016 ). Epigenetic activity chemically alters the chromatin (for example, modifications, including methylation and acetylation status of DNA, histones and transcriptional regulators) and brings about cell-, tissue
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Introduction Modification of DNA by cytosine methylation is an important mechanism of epigenetic regulation of genomic functions ( Zingg & Jones 1997 , Jaenisch & Bird 2003 ). DNA methylation patterns are mosaics in various cell and
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S -adenosyl- l -methionine to the guanidino nitrogens of arginine residues to form ω- N G , N G -asymmetric dimethyl-arginine (aDMA; Cheng et al . 2007 ). PRMT4 has also been shown to catalyze the methylation of specific arginine residues in the N
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We have previously examined the regulatory region of the mouse lactoferrin gene and have identified sequences essential for basal and hormonally induced expression. In this study, we explore the relationship between the methylation state of the mouse lactoferrin gene promoter and its expression in selected mouse tissues. In a transient expression system, transcriptional activity was blocked after in vitro methylation of the regulatory region of the mouse lactoferrin gene. In addition, the in vivo methylation state of three promoter region sites was assessed using Southern blot analysis of DNA digested with methylation-insensitive and -sensitive restriction enzymes. The results showed that site -455, upstream of the mouse lactoferrin estrogen response module, was highly unmethylated in DNA from both hormone-treated and -untreated mouse lung, liver, and spleen tissues. Also, in both treated and untreated samples, the -54 site is uniquely highly unmethylated in liver DNA, while the -22 site is unmethylated in spleen DNA. Northern blot analysis showed lactoferrin expression in tissues that were unmethylated at a minimum of two sites. These results show that the alteration of the methylation status of the three sites are tissue-specific and are associated with constitutive expression of lactoferrin.
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ABSTRACT
The pro-opiomelanocortin gene is widely expressed in human tissues, although both transcriptional initiation sites and regulation appear to be tissue specific. In order to determine how promoter and enhancer choice is effected, we have studied the methylation pattern of the gene in a number of normal tissues, tumours and cell lines. Variability of this pattern was observed in the 5′-flanking DNA, particularly at the HpaII site located at −304 bp upstream from the pituitary CAP site. This site was generally methylated in tissues likely to express the predominant extrapituitary (800 nucleotide) message, while in tissues known to express the normal pituitary (1150 nucleotide) message and longer species, a tendency towards undermethylation was observed. Although the sites at which variable methylation occurs did not correspond to established binding sites for regulatory proteins, many of these regions remain to be determined and thus it is possible that methylation may be influential in the tissue-specific regulation of this gene.
