|
| Status |
Public on Oct 04, 2018 |
| Title |
TET2 coactivates gene expression through demethylation of enhancers |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
|
| Summary |
The tet methylcytosine dioxygenase 2 (TET2) enzyme catalyzes the conversion of the modified DNA base 5-methylcytosine to 5-hydroxymethylcytosine. TET2 is frequently mutated or dysregulated in multiple human cancers, and loss of TET2 is associated with changes in DNA methylation patterns. Here, using newly developed TET2-specific antibodies and the estrogen response as a model system for studying the regulation of gene expression, we demonstrate that endogenous TET2 occupies active enhancers and facilitates the proper recruitment of ERalpha. Knockout of TET2 by CRISPR-CAS9 leads to a global increase of DNA-methylation at enhancers resulting in attenuation of the estrogen response. We further identified a positive feedback loop between TET2 and ERalpha, which further requires MLL3/COMPASS at these enhancers. Together, this study reveals an epigenetic axis coordinating a transcriptional program through enhancer activation via DNA demethylation.
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| |
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| Overall design |
To examine changes in histone modifications, ER-alpha occupancy, MLL3 occupancy, and gene expression changes after depletion of TET2 in human breast cancer cell lines.
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| |
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| Contributor(s) |
Wang L, Ozark PA, Shilatifard A |
| Citation(s) |
30417100 |
| Submission date |
Oct 02, 2018 |
| Last update date |
Mar 26, 2019 |
| Contact name |
Ali Shilatifard |
| E-mail(s) |
ash@northwestern.edu
|
| Organization name |
Northwestern University Feinberg School of Medicine
|
| Department |
Department of Biochemistry and Molecular Genetics
|
| Lab |
Shilatifard Lab
|
| Street address |
320 E Superior St
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (79)
|
|
| Relations |
| BioProject |
PRJNA494397 |
| SRA |
SRP163132 |
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