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| Status |
Public on Jan 01, 2016 |
| Title |
Allele-specific regulation of gene expression through enhancer function and transcriptional elongation control at imprinted loci |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Other
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| Summary |
Genomic imprinting is a critical developmental process characteristic of parent-of-origin- specific gene expression. Here, we have identified the AFF family protein, Aff3, as a factor that functionally interacts with imprinted loci. Indeed, our genome-wide studies demonstrate that Aff3 specifically binds both imprinting control regions (ICRs) and enhancers within imprinted loci in an allele-specific manner. We have identified the molecular regulators involved in the recruitment of Aff3 to ICRs to impede transcription through the ICR, and provide a mechanism requiring Aff3 within the Super Elongation Complex-like 3 (SEC-L3) in the expression of an imprinted polycistronic transcript spanning the Dlk1-Dio3 locus. Our study also shows that DNA methylation at the ICR reinforces silencing of its related enhancers by controlling the binding and activity of Aff3 in an allele-specific manner. This study provides molecular details about the regulation of dosage-critical imprinted gene expression through Aff3’s function in transcriptional elongation control.
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| Overall design |
ChIP-seq of Aff3 in different mES cells. ChIP-seq of Aff3, PolII, H3K9me3 in uniparental MEF cell lines. ChIP-seq of H3K27ac and PolII in mES cells after Aff3 shRNA and non-targeting shRNA. ChIP-seq of H3K27ac in wild type and Zfp57 knockout ES cells. Total RNA-seq and nascent RNA-seq of mES cells after Aff3 shRNA and non-targeting shRNA. Total RNA-seq of uniparental MEF cells after Aff3 shRNA and non-targeting shRNA.
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| Contributor(s) |
Luo Z, Gao X, Shilatifard A |
| Citation(s) |
26728555 |
| |
| Submission date |
Dec 23, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Joan Conaway |
| E-mail(s) |
JLC@stowers.org
|
| Organization name |
Stowers Institute
|
| Street address |
1000 E 50th ST
|
| City |
Kansas City |
| State/province |
MO |
| ZIP/Postal code |
64110 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (53)
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| Relations |
| BioProject |
PRJNA271109 |
| SRA |
SRP051521 |
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