|
Status |
Public on May 07, 2020 |
Title |
Epigenetic deregulation of lamina-associated domains in Hutchinson-Gilford Progeria Syndrome |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by genome tiling array
|
Summary |
Hutchinson-Gilford Progeria Syndrome (HGPS) is a progeroid disease characterized by the early onset of some classically age-related phenotypes including arthritis, loss of body fat and hair and atherosclerosis. Cells from affected individuals express a mutant version of the nuclear envelope protein Lamin A (termed Progerin) and have previously been shown to exhibit prominent chromatin changes. Here, we identify epigenetic deregulation of lamina-associated domains (LADs) as a central feature in the molecular pathology of HGPS. Using ATAC-see/-seq and Infinium MethylationEPIC BeadChip-mediated DNA methylation profiling, we demonstrate that dermal fibroblasts from HGPS patients exhibit both chromatin accessibility and DNA methylation changes that are enriched in LADs. Importantly, we further show that these epigenetic alterations are associated with HGPS-specific gene expression changes. Together, our results establish a central involvement of LADs in the epigenetic deregulation of HGPS and provide novel insight into the molecular changes associated with the disease.
|
|
|
Overall design |
Bisulphite converted DNA from the 15 samples were hybridized to the Illumina Infinium Human MethylationEPIC BeadChip
|
|
|
Contributor(s) |
Köhler F, Bormann F, Raddatz G, Gutekunst J, Musch T, Lyko F, Rodriguez-Paredes M |
Citation(s) |
32450911 |
Submission date |
May 06, 2020 |
Last update date |
Aug 06, 2020 |
Contact name |
Julian Gutekunst |
Organization name |
German Cancer Research Center
|
Street address |
Im Neuenheimer Feld 580
|
City |
Heidelberg |
ZIP/Postal code |
69124 |
Country |
Germany |
|
|
Platforms (1) |
GPL23976 |
Illumina Infinium HumanMethylation850 BeadChip |
|
Samples (15)
|
|
Relations |
BioProject |
PRJNA630703 |