UNIGE document Scientific Article
previous document  unige:43615  next document
add to browser collection

DNA sequence explains seemingly disordered methylation levels in partially methylated domains of Mammalian genomes

Gaidatzis, Dimos
Burger, Lukas
Lerch, Anita
Dessus-Babus, Sophie
Schübeler, Dirk
Stadler, Michael B
Published in PLOS Genetics. 2014, vol. 10, no. 2, p. e1004143
Abstract For the most part metazoan genomes are highly methylated and harbor only small regions with low or absent methylation. In contrast, partially methylated domains (PMDs), recently discovered in a variety of cell lines and tissues, do not fit this paradigm as they show partial methylation for large portions (20%-40%) of the genome. While in PMDs methylation levels are reduced on average, we found that at single CpG resolution, they show extensive variability along the genome outside of CpG islands and DNase I hypersensitive sites (DHS). Methylation levels range from 0% to 100% in a roughly uniform fashion with only little similarity between neighboring CpGs. A comparison of various PMD-containing methylomes showed that these seemingly disordered states of methylation are strongly conserved across cell types for virtually every PMD. Comparative sequence analysis suggests that DNA sequence is a major determinant of these methylation states. This is further substantiated by a purely sequence based model which can predict 31% (R(2)) of the variation in methylation. The model revealed CpG density as the main driving feature promoting methylation, opposite to what has been shown for CpG islands, followed by various dinucleotides immediately flanking the CpG and a minor contribution from sequence preferences reflecting nucleosome positioning. Taken together we provide a reinterpretation for the nucleotide-specific methylation levels observed in PMDs, demonstrate their conservation across tissues and suggest that they are mainly determined by specific DNA sequence features.
PMID: 24550741
Full text
Article (Published version) (1.5 MB) - public document Free access
Research group Epigénétique et développement (950)
(ISO format)
GAIDATZIS, Dimos et al. DNA sequence explains seemingly disordered methylation levels in partially methylated domains of Mammalian genomes. In: PLOS Genetics, 2014, vol. 10, n° 2, p. e1004143. doi: 10.1371/journal.pgen.1004143 https://archive-ouverte.unige.ch/unige:43615

459 hits



Deposited on : 2014-12-17

Export document
Format :
Citation style :