 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Oct 30, 2012 |
| Title |
Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome (ChIP-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease that is frequently caused by a de novo point mutation at position 1824 in LMNA. This mutation activates a cryptic splice donor site in exon 11, and leads to an in-frame deletion within the prelamin A mRNA and the production of a dominant negative lamin A protein, known as progerin. Here we show that HGPS cells experience genome-wide alterations in patterns of H3K27me3 deposition, changes in the associations of genomic loci with nuclear lamin A/C, and, at late passages, genome-wide loss of spatial compartmentalization of active and inactive chromatin domains that characterizes chromosome folding in normal cells. We further demonstrate that the H3K27me3 changes associate with gene expression alterations in HGPS cells. Our results support a model that the accumulation of progerin in the nuclear lamina leads to altered H3K27me3 marks in heterochromatin, possibly through the down-regulation of EZH2, and disrupts heterochromatin-lamina interactions. These changes may then lead to the genomic disorganization and changes in transcriptional regulation we observe in HGPS fibroblasts.
|
| |
|
| Overall design |
ChIP-Seq was performed for H3K27me3 and lamin A/C in the human genome in three primary fibroblast cell lines: an HGPS patient (HGPS), normal cells from the father of the HGPS patient (Father), and age-matched normal cells (Age Control). Two biological replicates were performed.
|
| |
|
| Contributor(s) |
McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, Erdos MR, Collins FS, Dekker J, Cao K |
| Citation(s) |
23152449 |
| |
| Submission date |
Oct 22, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Rachel Patton McCord |
| E-mail(s) |
Rachel.McCord@umassmed.edu
|
| Phone |
508-856-4377
|
| Organization name |
University of Massachusetts Medical School
|
| Department |
Program in Gene Function and Expression
|
| Lab |
Job Dekker Lab
|
| Street address |
364 Plantation St. LRB 570M
|
| City |
Worcester |
| State/province |
MA |
| ZIP/Postal code |
01605 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
|
| Samples (18)
|
| GSM1023613 |
H3K27me3 ChIP, Father, p19, INPUT |
| GSM1023614 |
H3K27me3 ChIP, Age Control, p17 |
| GSM1023615 |
H3K27me3 ChIP, Age Control, p17, INPUT |
| GSM1023616 |
H3K27me3 ChIP, HGPS, p14 |
| GSM1023617 |
H3K27me3 ChIP, HGPS, p14, INPUT |
| GSM1023618 |
H3K27me3 ChIP, HGPS, p17 |
| GSM1023619 |
H3K27me3 ChIP, HGPS, p17, INPUT |
| GSM1023620 |
LaminA ChIP, Father, p16, rep1 |
| GSM1023621 |
LaminA ChIP, Father, p16, INPUT, rep1 |
| GSM1023622 |
LaminA ChIP, Father, p16, rep2 |
| GSM1023623 |
LaminA ChIP, Father, p16, INPUT, rep2 |
| GSM1023624 |
LaminA ChIP, HGPS, p16, rep1 |
| GSM1023625 |
LaminA ChIP, HGPS, p16, INPUT, rep1 |
| GSM1023626 |
LaminA ChIP, HGPS, p16, rep2 |
| GSM1023627 |
LaminA ChIP, HGPS, p16, INPUT, rep2 |
|
| This SubSeries is part of SuperSeries: |
| GSE41764 |
Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome |
|
| Relations |
| BioProject |
PRJNA178125 |
| SRA |
SRP016587 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE41757_RAW.tar |
6.3 Gb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...