Impact of DNA methylation on 3D genome structure.
5' Untranslated Regions
/ genetics
Centromere
/ metabolism
Chromatin
/ metabolism
Chromatin Assembly and Disassembly
DNA (Cytosine-5-)-Methyltransferase 1
/ genetics
DNA (Cytosine-5-)-Methyltransferases
/ genetics
DNA Methylation
DNA Methyltransferase 3A
Epigenesis, Genetic
Genome, Fungal
Histones
/ genetics
Intravital Microscopy
Mutagenesis, Site-Directed
Mutation
Nucleosomes
/ genetics
RNA-Seq
Recombinant Proteins
/ genetics
Repressor Proteins
/ genetics
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
Whole Genome Sequencing
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 05 2021
28 05 2021
Historique:
received:
17
06
2020
accepted:
13
04
2021
entrez:
29
5
2021
pubmed:
30
5
2021
medline:
9
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34050148
doi: 10.1038/s41467-021-23142-8
pii: 10.1038/s41467-021-23142-8
pmc: PMC8163762
doi:
Substances chimiques
5' Untranslated Regions
0
Chromatin
0
Histones
0
Nucleosomes
0
Recombinant Proteins
0
Repressor Proteins
0
Saccharomyces cerevisiae Proteins
0
UME6 protein, S cerevisiae
0
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
DNA (Cytosine-5-)-Methyltransferases
EC 2.1.1.37
DNA Methyltransferase 3A
EC 2.1.1.37
Dnmt1 protein, mouse
EC 2.1.1.37
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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