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Status |
Public on Oct 30, 2015 |
Title |
Ataxia-telangiectasia cerebellar cortex expression |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Cerebellar cortex expression in ataxia-telangiectasia patients and normal controls.
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.
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Overall design |
Human frozen tissue was obtained from the NICHD Brain and Tissue Bank of Developmental Disorders at the University of Maryland, Baltimore, MD. RNA was prepared and run on an Illumina Human HT-12 v4 microarray. 3 ataxia-telangiectasia (A-T) cases and 4 normal controls.
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Contributor(s) |
Hart RP, Li J, Herrup K |
Citation(s) |
26510954, 27538496 |
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Submission date |
Sep 02, 2014 |
Last update date |
Mar 30, 2020 |
Contact name |
Ronald P. Hart |
E-mail(s) |
rhart@rutgers.edu
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Phone |
848-445-1783
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Organization name |
Rutgers University
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Department |
Cell Biology & Neuroscience
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Street address |
604 Allison Rd Rm B430
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City |
Piscataway |
State/province |
NJ |
ZIP/Postal code |
08854 |
Country |
USA |
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Platforms (1) |
GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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Samples (7)
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This SubSeries is part of SuperSeries: |
GSE61169 |
Selective loss of 5hmC links to A-T Purkinje cell vulnerability |
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Relations |
BioProject |
PRJNA260081 |
Supplementary file |
Size |
Download |
File type/resource |
GSE61019_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
GSE61019_non-normalized.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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