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Impact of DNA methylation on 3D genome structure.
- Source :
-
Nature communications [Nat Commun] 2021 May 28; Vol. 12 (1), pp. 3243. Date of Electronic Publication: 2021 May 28. - Publication Year :
- 2021
-
Abstract
- Determining the effect of DNA methylation on chromatin structure and function in higher organisms is challenging due to the extreme complexity of epigenetic regulation. We studied a simpler model system, budding yeast, that lacks DNA methylation machinery making it a perfect model system to study the intrinsic role of DNA methylation in chromatin structure and function. We expressed the murine DNA methyltransferases in Saccharomyces cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization. Despite lacking the machinery for positioning and reading methylation marks, induced DNA methylation follows a conserved pattern with low methylation levels at the 5' end of the gene increasing gradually toward the 3' end, with concentration of methylated DNA in linkers and nucleosome free regions, and with actively expressed genes showing low and high levels of methylation at transcription start and terminating sites respectively, mimicking the patterns seen in mammals. We also see that DNA methylation increases chromatin condensation in peri-centromeric regions, decreases overall DNA flexibility, and favors the heterochromatin state. Taken together, these results demonstrate that methylation intrinsically modulates chromatin structure and function even in the absence of cellular machinery evolved to recognize and process the methylation signal.
- Subjects :
- 5' Untranslated Regions genetics
Centromere metabolism
Chromatin metabolism
DNA (Cytosine-5-)-Methyltransferase 1 genetics
DNA (Cytosine-5-)-Methyltransferase 1 metabolism
DNA (Cytosine-5-)-Methyltransferases genetics
DNA (Cytosine-5-)-Methyltransferases metabolism
DNA Methyltransferase 3A
Genome, Fungal
Histones genetics
Histones metabolism
Intravital Microscopy
Mutagenesis, Site-Directed
Mutation
Nucleosomes genetics
RNA-Seq
Recombinant Proteins genetics
Recombinant Proteins isolation & purification
Recombinant Proteins metabolism
Repressor Proteins genetics
Repressor Proteins isolation & purification
Repressor Proteins metabolism
Saccharomyces cerevisiae Proteins genetics
Saccharomyces cerevisiae Proteins isolation & purification
Saccharomyces cerevisiae Proteins metabolism
Whole Genome Sequencing
Chromatin Assembly and Disassembly
DNA Methylation
Epigenesis, Genetic
Nucleosomes metabolism
Saccharomyces cerevisiae genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 34050148
- Full Text :
- https://doi.org/10.1038/s41467-021-23142-8