Abstract
5-hydroxymethylcytosine (5-hmC) is a modified form of cytosine recently found in mammalians and is believed, like 5-methylcytosine, to also play an important role in switching genes on and off. By utilizing a newly developed 5-hmC immunoassay, we determined the abundance of 5-hmC in human tissues and compared 5-hmC states in normal colorectal tissue and cancerous colorectal tissue. Significant differences of 5-hmC content in different tissues were observed. The percentage of 5-hmC measured is high in brain, liver, kidney and colorectal tissues (0.40–0.65%), while it is relatively low in lung (0.18%) and very low in heart, breast, and placenta (0.05-0.06%). Abundance of 5-hmC in the cancerous colorectal tissues was significantly reduced (0.02–0.06%) compared to that in normal colorectal tissues (0.46–0.57%). Our results showed for the first time that 5-hmC distribution is tissue dependent in human tissues and its abundance could be changed in the diseased states such as colorectal cancer.
Highlights
DNA methylation is an epigenetic modification which is catalyzed by DNA cytosine-5-methyltransferases (DNMTs) and occurs at the 5-position (C5) of the cytosine ring, within CpG dinucleotides
Region-specific DNA methylation is mainly found in 5 -CpG-3 dinucleotides within the promoters or in the first exon of genes, which is an important pathway for the repression of gene transcription in diseased cells
To the best of our knowledge, this is the first paper of 5-hmC distribution in different human tissues and 5-hmC status in solid tumor
Summary
DNA methylation is an epigenetic modification which is catalyzed by DNA cytosine-5-methyltransferases (DNMTs) and occurs at the 5-position (C5) of the cytosine ring, within CpG dinucleotides. Region-specific DNA methylation is mainly found in 5 -CpG-3 dinucleotides within the promoters or in the first exon of genes, which is an important pathway for the repression of gene transcription in diseased cells. 5-hmC is a hydroxylated and methylated form of cytosine and was first seen in bacteriophages in 1952 [7]. In mammals, it can be generated by a TET protein-mediated reaction [5]. 5-hmC might play an important and different role in regulation of DNA methylation, chromatin remodeling, and gene expression in a tissue-, cell-, or organ-specific manner
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