Epigenetic memory via concordant DNA methylation is inversely correlated to developmental potential of mammalian cells
| Autor: | Haneen Al-Azzawi, Jamie M. Goodson, Daniel G. Miller, Noah Simon, Minseung Choi, Stan Palasek, Diane P. Genereux, Kevin D. Sinclair, Shannon Q. Allain, Reinhard Stöger, Winslow C. Johnson, Chris Cavanaugh, Carol B. Ware, Charles D. Laird |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cancer Research Cellular differentiation Artificial Gene Amplification and Extension Biochemistry Polymerase Chain Reaction Epigenesis Genetic Mice chemistry.chemical_compound 0302 clinical medicine Animal Cells Induced pluripotent stem cell Cells Cultured Genetics (clinical) Epigenesis 0303 health sciences DNA methylation Stem Cells Chemical Reactions Nuclear Proteins Cell Differentiation Methylation Chromatin Nucleic acids Chemistry 030220 oncology & carcinogenesis Physical Sciences Female Epigenetics Cellular Types Stem cell DNA modification Chromatin modification Research Article Chromosome biology DNA (Cytosine-5-)-Methyltransferase 1 DNA Replication Cell biology lcsh:QH426-470 Ubiquitin-Protein Ligases Biology Research and Analysis Methods 03 medical and health sciences Genetics Animals Humans Molecular Biology Techniques Molecular Biology Embryonic Stem Cells Ecology Evolution Behavior and Systematics 030304 developmental biology Biology and life sciences DNA replication DNA Fibroblasts Repressor Proteins lcsh:Genetics 030104 developmental biology chemistry Genetic Loci Evolutionary biology CCAAT-Enhancer-Binding Proteins Gene expression Developmental Biology |
| Zdroj: | PLoS Genetics, Vol 13, Iss 11, p e1007060 (2017) PLoS Genetics |
| ISSN: | 1553-7404 |
| Popis: | In storing and transmitting epigenetic information, organisms must balance the need to maintain information about past conditions with the capacity to respond to information in their current and future environments. Some of this information is encoded by DNA methylation, which can be transmitted with variable fidelity from parent to daughter strand. High fidelity confers strong pattern matching between the strands of individual DNA molecules and thus pattern stability over rounds of DNA replication; lower fidelity confers reduced pattern matching, and thus greater flexibility. Here, we present a new conceptual framework, Ratio of Concordance Preference (RCP), that uses double-stranded methylation data to quantify the flexibility and stability of the system that gave rise to a given set of patterns. We find that differentiated mammalian cells operate with high DNA methylation stability, consistent with earlier reports. Stem cells in culture and in embryos, in contrast, operate with reduced, albeit significant, methylation stability. We conclude that preference for concordant DNA methylation is a consistent mode of information transfer, and thus provides epigenetic stability across cell divisions, even in stem cells and those undergoing developmental transitions. Broader application of our RCP framework will permit comparison of epigenetic-information systems across cells, developmental stages, and organisms whose methylation machineries differ substantially or are not yet well understood. Author summary As stem cells differentiate, they acquire epigenetic marks that activate some genes and silence others, eventually producing the profiles that define specific cell lineages. While existing approaches can reveal the differentiation state of a given cell or the activity state of a given gene, none can locate an individual genomic region along the epigenetic continuum between flexible and fixed. To address this challenge, we introduce a new framework to infer epigenetic stability from the concordance of DNA methylation patterns on the two strands of individual DNA molecules. For cells of all developmental potentials, we find that top- and bottom-strand methylation patterns match far more often than expected by chance alone. As cells differentiate, the fidelity of pattern transfer increases, thereby resulting in higher epigenetic stability; dedifferentiation is characterized by declining stability. Our metric has the potential to identify genomic regions that remain sensitive to environmental signals well beyond the interval of lineage specification. |
| Databáze: | OpenAIRE |
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