|
| Status |
Public on Oct 30, 2015 |
| Title |
MeDIP analysis of 5mC and 5hmC marks in human ataxia-telangiectasia cerebellum |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Genomic DNA was prepared, fragmented, and immunoprecipitated with antibodies specific for 5mC or 5hmC prior to standard sequencing.
The neurodegenerative disease known as ataxia-telangiectasia (A-T) is caused by the absence of the ATM (A-T mutated) protein. A long-standing mystery surrounding A-T is why cerebellar Purkinje cells (PCs) appear uniquely vulnerable to ATM-deficiency. Here, we present that 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic marker found at high levels in neurons, is substantially reduced in human A-T and Atm-/- mouse cerebellar PCs. TET1, an enzyme that converts 5mC to 5hmC, responds to DNA damage. Manipulation of TET1 activity directly affects neuronal cell cycle reentry and cell death after the induction of DNA damage. Quantitative, genome-wide analysis of 5hmC of samples from human cerebellum showed that in ATM-deficiency there is a remarkable genome-wide reduction of 5hmC enrichment at both proximal and distal regulatory elements. These results reveal a role of TET1-mediated 5hmC in DNA damage response, and provide insights into the basis of a PC-specific DNA demethylation alteration in ATM-deficiency.
|
| |
|
| Overall design |
There are two groups, A-T and Control. For each group, cerebellar DNA samples were immunoprecipitated with anti-5mC (n=1) or anti-5hmC (n=3). There were also two replicates of input control for each group.
|
| |
|
| Contributor(s) |
Hart RP, Li J, Herrup K |
| Citation(s) |
26510954 |
| Submission date |
Sep 04, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Ronald P. Hart |
| E-mail(s) |
rhart@rutgers.edu
|
| Phone |
848-445-1783
|
| Organization name |
Rutgers University
|
| Department |
Cell Biology & Neuroscience
|
| Street address |
604 Allison Rd Rm B430
|
| City |
Piscataway |
| State/province |
NJ |
| ZIP/Postal code |
08854 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (12)
|
|
| This SubSeries is part of SuperSeries: |
| GSE61169 |
Selective loss of 5hmC links to A-T Purkinje cell vulnerability |
|
| Relations |
| BioProject |
PRJNA260309 |
| SRA |
SRP046261 |
Less...
More...