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Series GSE41763 Query DataSets for GSE41763
Status Public on Oct 30, 2012
Title Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome (Hi-C)
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 Hi-C was performed on three primary fibroblast cell lines: an HGPS patient (passage 17 and 19; HGPS), normal cells from the father of the HGPS patient (passage 18; Father), and age-matched normal cells (passage 20; Age Control).
 
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)
GPL9115 Illumina Genome Analyzer II (Homo sapiens)
Samples (4)
GSM1023732 Hi-C Normal Father Fibroblasts p18
GSM1023733 Hi-C Normal Age-Control Fibroblasts p20
GSM1023734 Hi-C Progeria (HGPS) Fibroblasts p17
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 PRJNA178126
SRA SRP016586

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE41763_RAW.tar 1.4 Gb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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