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| Status |
Public on Jul 20, 2022 |
| Title |
DNA sequence determines epigenetic bistability at imprinting control regions [BS-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Genomic imprinting is regulated by parental-specific epigenetic marks that differentiate between maternal and paternal chromosomes. Despite identical DNA sequence, the presence or absence of DNA methylation leads to the establishment of two distinct epigenetic states at Imprinting Control Regions (ICR). Here we combine targeted epigenome engineering to generate ectopic loci in the mouse embryonic stem cell genome that recapitulate the epigenetic properties of ICRs. We describe these ectopic ICRs as strong cis-regulatory sequences that can adopt and memorise one of two opposing epigenetic states, dependent of pre-imposed DNA methylation. This bistability is unique to ICRs and enabled us to systematically study the genetic and epigenetic determinants required for creating and maintaining the observed states. Through sequence manipulation we show that the ICR DNA sequence confers autonomy of ICRs and is required for creating epigenetic bistability. Genetic screens using DNA-methylation-sensitive reporters identify key components involved in regulating maintenance of epigenetic states. Besides DNMT1, UHRF1 and ZFP57, we identify novel factors that prevent switching between methylated and unmethylated states and validate two of these candidates, ATF7IP and ZMYM2, to be important for epigenetic memory at ICRs. In summary we show that the DNA sequence of ICRs provides the prerequisite for establishment of two distinct epigenetic states, while DNA and histone modifications ensure their stable propagation.
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| Overall design |
Targeted bisulfite sequencing for Airn, Kcnq1ot1 and Peg10 ICRs in wild type and Atf7ip KO cells
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| Contributor(s) |
Baubec T, Butz S |
| Citation missing |
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| |
| Submission date |
Jun 09, 2021 |
| Last update date |
Jul 23, 2022 |
| Contact name |
Tuncay Baubec |
| Organization name |
Utrecht University
|
| Department |
Department of Biology
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| Lab |
Genome Biology and Epigenetics
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| Street address |
Padualaan 8
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| City |
Utrecht |
| ZIP/Postal code |
3584 CH |
| Country |
Netherlands |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE176461 |
DNA sequence and chromatin modifiers determine epigenetic bistability at imprinting control regions |
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| Relations |
| BioProject |
PRJNA736334 |
| SRA |
SRP323367 |
