ATAC-Me Captures Prolonged DNA Methylation of Dynamic Chromatin Accessibility Loci during Cell Fate Transitions
| Autor: | Emily Hodges, Jonathan Attalla, Kelly R. Barnett, Benjamin E. Decato, Andrew D. Smith, Bob Chen, Timothy J. Scott, Tyler J. Hansen |
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| Rok vydání: | 2019 |
| Předmět: |
Cellular differentiation
Computational biology Biology Regulatory Sequences Nucleic Acid Monocytes 03 medical and health sciences 0302 clinical medicine Humans Cell Lineage Gene Regulatory Networks Epigenetics Enhancer Molecular Biology Gene 030304 developmental biology Regulation of gene expression 0303 health sciences Binding Sites Macrophages Gene Expression Regulation Developmental High-Throughput Nucleotide Sequencing Cell Differentiation Cell Biology Methylation DNA Methylation Cellular Reprogramming Chromatin DNA methylation 030217 neurology & neurosurgery |
| Zdroj: | Molecular cell. 77(6) |
| ISSN: | 1097-4164 |
| Popis: | Summary DNA methylation of enhancers is dynamic, cell-type specific, and vital for cell fate progression. However, current models inadequately define its role within the hierarchy of gene regulation. Analysis of independent datasets shows an unanticipated overlap between DNA methylation and chromatin accessibility at enhancers of steady-state stem cells, suggesting that these two opposing features might exist concurrently. To define their temporal relationship, we developed ATAC-Me, which probes accessibility and methylation from single DNA library preparations. We identified waves of accessibility occurring rapidly across thousands of myeloid enhancers in a monocyte-to-macrophage cell fate model. Prolonged methylation states were observed at a majority of these sites, while transcription of nearby genes tracked closely with accessibility. ATAC-Me uncovers a significant disconnect between chromatin accessibility, DNA methylation status, and gene activity. This unexpected observation highlights the value of ATAC-Me in constructing precise molecular timelines for understanding the role of DNA methylation in gene regulation. |
| Databáze: | OpenAIRE |
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