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- W1878377624 endingPage "3169" @default.
- W1878377624 startingPage "3155" @default.
- W1878377624 abstract "In mammals, the cytosine in CG dinucleotides is typically methylated producing 5-methylcytosine (5mC), a chemically less stable form of cytosine that can spontaneously deaminate to thymidine resulting in a T•G mismatched base pair. Unlike other eukaryotes that efficiently repair this mismatched base pair back to C•G, in mammals, 5mCG deamination is mutagenic, sometimes producing TG dinucleotides, explaining the depletion of CG dinucleotides in mammalian genomes. It was suggested that new TG dinucleotides generate genetic diversity that may be critical for evolutionary change. We tested this conjecture by examining the DNA sequence properties of regulatory sequences identified by DNase I hypersensitive sites (DHSs) in human and mouse genomes. We hypothesized that the new TG dinucleotides generate transcription factor binding sites (TFBS) that become tissue-specific DHSs (TS-DHSs). We find that 8-mers containing the CG dinucleotide are enriched in DHSs in both species. However, 8-mers containing a TG and no CG dinucleotide are preferentially enriched in TS-DHSs when compared with 8-mers with neither a TG nor a CG dinucleotide. The most enriched 8-mer with a TG and no CG dinucleotide in tissue-specific regulatory regions in both genomes is the AP-1 motif ( TG: A(C)/GT CA: N), and we find evidence that TG dinucleotides in the AP-1 motif arose from CG dinucleotides. Additional TS-DHS-enriched TFBS containing the TG/CA dinucleotide are the E-Box motif (G CA: GC TG: C), the NF-1 motif (GG CATG: CC), and the GR (glucocorticoid receptor) motif (G-A CATG: T-C). Our results support the suggestion that cytosine methylation is mutagenic in tetrapods producing TG dinucleotides that create TFBS that drive evolution." @default.
- W1878377624 created "2016-06-24" @default.
- W1878377624 creator A5006847496 @default.
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- W1878377624 creator A5059640675 @default.
- W1878377624 creator A5066194289 @default.
- W1878377624 creator A5082279528 @default.
- W1878377624 date "2015-10-27" @default.
- W1878377624 modified "2023-10-11" @default.
- W1878377624 title "Methylated Cytosines Mutate to Transcription Factor Binding Sites that Drive Tetrapod Evolution" @default.
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- W1878377624 doi "https://doi.org/10.1093/gbe/evv205" @default.
- W1878377624 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4994754" @default.