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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 14, 2022 |
| Title |
Long-range phasing of dynamic, tissue-specific and allele-specific regulatory elements |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
Methylation profiling by high throughput sequencing
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| Summary |
Epigenomic maps identify gene regulatory elements by their chromatin state. However, prevailing short-read sequencing methods cannot effectively distinguish alleles, evaluate the interdependence of elements in a locus or capture single-molecule dynamics. Here, we apply targeted nanopore sequencing to profile chromatin accessibility and DNA methylation on contiguous ~100-kb DNA molecules that span loci relevant to development, immunity and imprinting. We detect promoters, enhancers, insulators and transcription factor footprints on single molecules based on exogenous GpC methylation. We infer relationships among dynamic elements within immune loci, and order successive remodeling events during T cell stimulation. Finally, we phase primary sequence and regulatory elements across the H19/IGF2 locus, uncovering primate-specific features. These include a segmental duplication that stabilizes the imprinting control region and a noncanonical enhancer that drives biallelic IGF2 expression in specific contexts. Our study advances emerging strategies for phasing gene regulatory landscapes and reveals a mechanism that overrides IGF2 imprinting in human cells.
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| Overall design |
targeted NOMe, RNA-seq and ATAC-seq were performed on cell lines and primary cells in resting or stimulated conditions.
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| Contributor(s) |
Battaglia S, Dong K, Wu J, Chen Z, Bernstein BE |
| Citation(s) |
36195755 |
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| Submission date |
Sep 09, 2021 |
| Last update date |
Oct 05, 2022 |
| Contact name |
Kevin Dong |
| Organization name |
Dana-Farber Cancer Institute
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| Street address |
360 Longwood Ave
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| City |
Boston |
| State/province |
MASSACHUSETTS |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (2) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA762003 |
| SRA |
SRP336359 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE183760_RAW.tar |
810.8 Mb |
(http)(custom) |
TAR (of BIGWIG, NARROWPEAK, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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