|
| Status |
Public on Jan 06, 2021 |
| Title |
WDR76 promotes MLL-rearranged leukemia via highly-selective binding of 5-hydroxymethylcytosine in DNA |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Although rare, the distribution of the 5-hydroxymethylcytosine (hmC) modification in mammalian DNA is tissue- and gene-specific, yet distinct from its repressive methylcytosine (mC) precursor, suggesting unique functions. To examine this possibility, we fractionated mammalian brain extracts to discover binding partners specific for oxidized states of mC. We demonstrate that one such factor, WDR76, is a highly hmC-specific binding protein that modulates gene expression within chromosomal regions enriched in hmC where it binds. In human cell lines and mouse models, WDR76 recruitment by hmC is critical for the initiation and maintenance of MLL-rearranged leukemias. Beyond its canonical role as an intermediate in mC remediation, we show that hmC can be an epigenetic mark whose recognition drives leukemogenesis, portending analogous signaling pathways for other rare DNA modifications.
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| |
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| Overall design |
ChiP-seq of epitope tagged WDR76 and RNA-seq of Wdr76 knockout in mouse embyrionic stem cells
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| |
|
| Contributor(s) |
Malecek KE, Weng H, Sullivan MA, Werner MS, Chen J, Ruthenburg AJ |
| Citation missing |
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| |
| Submission date |
Jan 05, 2018 |
| Last update date |
Jan 06, 2021 |
| Contact name |
Alexander Ruthenburg |
| E-mail(s) |
aruthenburg@uchicago.edu
|
| Organization name |
University of Chicago
|
| Department |
MGCB/BMB
|
| Lab |
Ruthenburg Lab
|
| Street address |
920 E 58th St, CLSC 855
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60637 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (8)
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|
| Relations |
| BioProject |
PRJNA428762 |
| SRA |
SRP128144 |
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