Dataset Information

C9orf72 promoter hypermethylation is reduced while hydroxymethylation is acquired during reprogramming of ALS patient cells.

ABSTRACT: Among several genetic mutations known to cause amyotrophic lateral sclerosis (ALS), a hexanucleotide repeat expansion in the C9orf72 gene is the most common. In approximately 30% of C9orf72-ALS cases, 5-methylcytosine (5mC) levels within the C9orf72 promoter are increased, resulting in a modestly attenuated phenotype. The developmental timing of C9orf72 promoter hypermethylation and the reason why it occurs in only a subset of patients remain unknown. In order to model the acquisition of C9orf72 hypermethylation and examine the potential role of 5-hydroxymethylcytosine (5hmC), we generated induced pluripotent stem cells (iPSCs) from an ALS patient with C9orf72 promoter hypermethylation. Our data show that 5mC levels are reduced by reprogramming and then re-acquired upon neuronal specification, while 5hmC levels increase following reprogramming and are highest in iPSCs and motor neurons. We confirmed the presence of 5hmC within the C9orf72 promoter in post-mortem brain tissues of hypermethylated patients. These findings show that iPSCs are a valuable model system for examining epigenetic perturbations caused by the C9orf72 mutation and reveal a potential role for cytosine demethylation.

SUBMITTER: Esanov R

PROVIDER: S-EPMC4761318 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

C9orf72 promoter hypermethylation is reduced while hydroxymethylation is acquired during reprogramming of ALS patient cells.

Esanov Rustam R Belle Kinsley C KC van Blitterswijk Marka M Belzil Veronique V VV Rademakers Rosa R Dickson Dennis W DW Petrucelli Leonard L Boylan Kevin B KB Dykxhoorn Derek M DM Wuu Joanne J Benatar Michael M Wahlestedt Claes C Zeier Zane Z

Experimental neurology 20151231

Among several genetic mutations known to cause amyotrophic lateral sclerosis (ALS), a hexanucleotide repeat expansion in the C9orf72 gene is the most common. In approximately 30% of C9orf72-ALS cases, 5-methylcytosine (5mC) levels within the C9orf72 promoter are increased, resulting in a modestly attenuated phenotype. The developmental timing of C9orf72 promoter hypermethylation and the reason why it occurs in only a subset of patients remain unknown. In order to model the acquisition of C9orf72 ...[more]

PMID: 26746986

Similar Datasets

Project description:Genome-wide microarray analyses revealed that during biological activation of systemic acquired resistance (SAR) in Arabidopsis, the transcript levels of several hundred plant genes were consistently up- (SAR(+) genes) or down-regulated (SAR(-) genes) in systemic, non-inoculated leaf tissue. This transcriptional reprogramming fully depended on the SAR regulator FLAVIN-DEPENDENT MONOOXYGENASE1 (FMO1). Functional gene categorization showed that genes associated with salicylic acid (SA)-associated defenses, signal transduction, transport, and the secretory machinery are overrepresented in the group of SAR(+) genes, and that the group of SAR(-) genes is enriched in genes activated via the jasmonate (JA)/ethylene (ET)-defense pathway, as well as in genes associated with cell wall remodeling and biosynthesis of constitutively produced secondary metabolites. This suggests that SAR-induced plants reallocate part of their physiological activity from vegetative growth towards SA-related defense activation. Alignment of the SAR expression data with other microarray information allowed us to define three clusters of SAR(+) genes. Cluster I consists of genes tightly regulated by SA. Cluster II genes can be expressed independently of SA, and this group is moderately enriched in H2O2- and abscisic acid (ABA)-responsive genes. The expression of the cluster III SAR(+) genes is partly SA-dependent. We propose that SA-independent signaling events in early stages of SAR activation enable the biosynthesis of SA and thus initiate SA-dependent SAR signaling. Both SA-independent and SA-dependent events tightly co-operate to realize SAR. SAR(+) genes function in the establishment of diverse resistance layers, in the direct execution of resistance against different (hemi-)biotrophic pathogen types, in suppression of the JA- and ABA-signaling pathways, in redox homeostasis, and in the containment of defense response activation. Our data further indicated that SAR-associated defense priming can be realized by partial pre-activation of particular defense pathways.

Dataset Information

C9orf72 promoter hypermethylation is reduced while hydroxymethylation is acquired during reprogramming of ALS patient cells.

Publications

C9orf72 promoter hypermethylation is reduced while hydroxymethylation is acquired during reprogramming of ALS patient cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets