%0 Journal Article
%T The Unexpected Existence of Coding and Non-Coding Fragments along the Eukaryotic Gene
%A Pietro Volpe
%J Advances in Biological Chemistry
%P 98-125
%@ 2162-2191
%D 2015
%I Scientific Research Publishing
%R 10.4236/abc.2015.52009
%X The pathways leading to synthesis and post-synthetic modification of DNA employed methionine as donor of atoms: the carbon that came from its ¨CCH3 served for DNA replication and repair either in bacteria or humans; its entire ¨CCH3 served instead for building N6-methyladenine and 5-methylcytosine on bacterial DNA and 5-methylcytosine alone on human DNA. In humans, although a slight extra-S asymmetric methylation appeared de novo yielding on parental DNA 5¡¯-m5CpC-3¡¯/ 3¡¯-GpG-5¡¯, 5¡¯-m5CpT-3¡¯/3¡¯-GpA-5¡¯ and 5¡¯-m5CpA-3¡¯/3¡¯-GpT-5¡¯ monomethylated dinucleotide pairs, a heavy symmetric methylation involved in S semiconservatively newly made DNA to guarantee genetic <i>maintenance</i> of ¨CCH3 in 5¡¯-m5CpG-3¡¯/3¡¯-Gpm5C-5¡¯ dimethylated dinucleotide pairs. In this framework, an inverse correlation was found between bulk genomic DNA methylation occurring in S and bulk polyA-containing pre-mRNA transcription taking place in G1 and G<sub>2</sub>. Thus, <i>probes</i> of 1 ¡Á 10<sup>6</sup> Daltons (constructed using sheared by sonication newly made methylated DNA filaments) revealed a modular organization in genes: after the hypermethylated promoter, they exhibited an alternation of unmethylated coding and methylated uncoding sequences. This encouraged the search for a language that genes regulated by methylation should have in common. An initial deciphering of <i>restriction minimaps</i> with hypomethylatable exons vs. hypermethylatable promoters and introns was improved when the bisulfite technique allowed a direct sequencing of m5C. In <i>lymphocytes</i>, where the transglutaminase gene is inactive, its promoter exhibited two fully methylated CpG-rich domains at 5¡¯ and one fully unmethylated CpG-rich domain at 3¡¯, including the site +1 and a 5¡¯-UTR. At variance, in <i>HUVEC</i> cells, where the transglutaminase gene is active, in the first CpG-rich domain of promoter few doublets lost their ¨CCH<sub>3</sub>. Such an inverse correlation suggested new hypotheses especially in connection with <i>repair-modification</i>: UV radiation would cause demethylation in given <i>loci</i> of a promoter by chance, whilst even a partial demethylation in this promoter would be able to resume a previously silent pre-mRNA transcription.
%K Coding vs. Non-Coding Pre-Messenger RNA Regions
%K Exons and Introns
%K Multigenic and Monogenic Transcriptional Units
%K Regulation of Gene Expression
%K Repair-Modification
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=55268