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Status |
Public on May 01, 2019 |
Title |
ATAC-Me captures spatiotemporal dynamics of DNA methylation across the chromatin accessible genome |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Methylation profiling by high throughput sequencing
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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 highly ordered steps of gene regulation. An analysis of independent datasets show an unanticipated overlap between DNA methylation and chromatin accessibility at enhancers of steady state stem cells, suggesting that two opposing features might exist concurrently. To temporally define the relationship between these two events, we developed ATAC-Me, which probes accessibility and methylation from a single library preparation. We identified waves of accessibility, both transient and persistent, occurring rapidly across thousands of myeloid enhancers as monocyte cells transition to a macrophage state. Persistent methylation states were observed at a majority of these sites while transcriptional responses 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.
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Overall design |
RNA-seq and ATAC-Me-seq libraries were generated for 5 time points of PMA stimulated THP-1 monocytes (0, 0.5, 1, 2, 24hrs), in biological replicate. Standard ATAC-seq libraries were generated at two time points (0, 24hr) in biological replicate. WGBS libraries were generated at two time points (0, 24 hr).
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Contributor(s) |
Barnett KR, Hodges EC |
Citation missing |
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Submission date |
Apr 19, 2019 |
Last update date |
May 03, 2019 |
Contact name |
Emily Hodges |
E-mail(s) |
emily.hodges@vanderbilt.edu
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Organization name |
Vanderbilt University
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Department |
Biochemistry
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Lab |
Hodges
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Street address |
2212 Garland Ave.
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City |
Nashville |
State/province |
TN |
ZIP/Postal code |
37232 |
Country |
USA |
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Platforms (4)
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GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
GPL20795 |
HiSeq X Ten (Homo sapiens) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (26)
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Relations |
BioProject |
PRJNA533829 |
SRA |
SRP193115 |