GEO DataSets

(Submitter supplied) The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is associated with mutation of the DNA methyl-transferase DNMT3B, resulting in a reduction of enzyme activity. Aberrant expression of immune system genes and hypomethylation of pericentromeric regions accompanied by chromosomal instability were determined as alterations driving the disease phenotype. However, so far only technologies capable of analyzing single loci were applied to determine epigenetic alterations in ICF patients. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL11154

2 Samples

Download data: TXT

(Submitter supplied) Genome-wide DNA methylation patterns are established and maintained by the coordinated action of three DNA methyltransferases, DNMT1, DNMT3A, and DNMT3B. DNMT3B hypomorphic germline mutations are responsible for two-thirds of Immunodeficiency, Centromere Instability, Facial Anomalies (ICF) syndrome cases. The molecular defects in transcription, DNA methylation, and chromatin structure in ICF cells remain relatively uncharacterized. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL97 GPL96

45 Samples

Download data: CEL, CHP, EXP

(Submitter supplied) Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. more...

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL13534

5 Samples

Download data: TXT

(Submitter supplied) DNA methylation differences between Newborns and Nonagenarians

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL13534

40 Samples

Download data: TXT

(Submitter supplied) DNA methyltransferase 3B (DNMT3B) is the major DNMT that methylates mammalian genomes during early development. Mutations in human DNMT3B disrupt genome-wide DNA methylation patterns and result in ICF syndrome type 1 (ICF1). To study whether normal DNA methylation patterns may be restored in ICF1 cells, we corrected DNMT3B mutations in induced pluripotent stem cells from ICF1 patients. Focusing on repetitive regions, we show that in contrast to pericentromeric repeats, which reacquire normal methylation, the majority of subtelomeres acquire only partial DNA methylation and, accordingly, the telomeric ICF1 phenotype persists. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL17301

195 Samples

Download data: BED

(Submitter supplied) DNA methyltransferase 3B (DNMT3B) is the major DNMT that methylates mammalian genomes during early development. Mutations in human DNMT3B disrupt genome-wide DNA methylation patterns and result in ICF syndrome type 1 (ICF1). To study whether normal DNA methylation patterns may be restored in ICF1 cells, we corrected DNMT3B mutations in induced pluripotent stem cells from ICF1 patients. Focusing on repetitive regions, we show that in contrast to pericentromeric repeats, which reacquire normal methylation, the majority of subtelomeres acquire only partial DNA methylation and, accordingly, the telomeric ICF1 phenotype persists. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL16791

7 Samples

Download data: BED

(Submitter supplied) Dysfunction of DNA methyltransferase 3b (DNMT3b) causes centromere instability but the underlying mechanism is unclear. We found that enforced expression of RNase H1 that removes R-loops, nucleic structures comprising an DNA-RNA hybrid, was sufficient to abolish DNA double-strand breaks (DSBs) at (peri-)centromeric sites in immunodeficiency-centromeric instability-facial anomalies (ICF) patient cells carrying DNMT3b mutation. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

3 Samples

Download data: TDF

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other; Genome binding/occupancy profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platforms:

GPL11154 GPL13393

40 Samples

Download data: BED, FPKM_TRACKING, TXT

(Submitter supplied) We performed a transcriptomic and epigenomic study in patient-derived B-cell lines to investigate the genome-scale effects of DNMT3B dysfunction. We highlighted that altered intragenic CpG-methylation impairs multiple aspects of transcriptional regulation, like alternative TSS usage, antisense transcription and exon splicing.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL13393 GPL11154

20 Samples

Download data: BED

(Submitter supplied) We performed a transcriptomic and epigenomic study in patient-derived B-cell lines to investigate the genome-scale effects of DNMT3B dysfunction. We highlighted that altered intragenic CpG-methylation impairs multiple aspects of transcriptional regulation, like alternative TSS usage, antisense transcription and exon splicing.

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: BED

(Submitter supplied) We performed a transcriptomic and epigenomic study in patient-derived B-cell lines to investigate the genome-scale effects of DNMT3B dysfunction. We highlighted that altered intragenic CpG-methylation impairs multiple aspects of transcriptional regulation, like alternative TSS usage, antisense transcription and exon splicing.

Organism:

Homo sapiens

Type:

Other

Platform:

GPL11154

8 Samples

Download data: FPKM_TRACKING

(Submitter supplied) We performed a transcriptomic and epigenomic study in patient-derived B-cell lines to investigate the genome-scale effects of DNMT3B dysfunction. We highlighted that altered intragenic CpG-methylation impairs multiple aspects of transcriptional regulation, like alternative TSS usage, antisense transcription and exon splicing.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

8 Samples

Download data: TXT

(Submitter supplied) Immunodeficiency, Centromeric Instability, and Facial Anomalies Type I (ICF1) Syndrome is a rare genetic disease caused by mutations in DNMT3B, a de novo DNA methyltransferase. However, the molecular basis of how DNMT3B-deficiency leads to ICF1 pathogenesis is unclear. Induced pluripotent stem cell (iPSC) technology facilitates the study of early human developmental diseases via facile in vitro paradigms. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platform:

GPL11154

7 Samples

Download data: BED, TXT

(Submitter supplied) Genome wide DNA methylation profiling of normal and ICF blood samples. The Illumina Infinium Human Methylation 450 BeadChip was used to obtain DNA methylation profiles across approximately 485,000 CpGs in whole blood from healthy and ICF subjects. Samples included 10 healthy subjects, 8 ICF1, 4 ICF2, 2 ICF3 and 1 ICF4 patients.

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL13534

25 Samples

Download data: TXT

(Submitter supplied) DNA methylation perturbations have been a hallmark of Immunodeficiency, Centromeric instability, Facial anomalies type I (ICF1) syndrome. The early developmental abnormalities due to DNMT3B deficiency accounts for genome-wide methylation defects that have been addressed frequently in many studies. Biallelic hypomorphic DNMT3B mutations cause the ICF1 syndrome. We have investigated the role of DNMT3B in mediating methylation at imprinted loci by employing induced pluripotent stem cells (iPSC) lines derived from ICF1 patients and their derivative strains in which the DNMT3B mutations were corrected by CRISPR/Cas9 technology. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL21145

10 Samples

Download data: IDAT, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platforms:

GPL16791 GPL18573 GPL24676

100 Samples

Download data: TXT

(Submitter supplied) Bi-allelic hypomorphic mutations in DNMT3B disrupt DNA methyltransferase activity and lead to Immunodeficiency, Centromeric instability, Facial anomalies syndrome, type 1 (ICF1). While several ICF1 phenotypes have been linked to abnormally hypomethylated repetitive regions, the unique genomic regions responsible for the remaining disease phenotypes remain largely uncharacterized. Here we explored two ICF1 patient-induced pluripotent stem cells (iPSCs) and their CRISPR-Cas9 corrected clones to determine whether DNMT3B correction can globally overcome DNA methylation defects and related changes in the epigenome. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL18573

7 Samples

Download data: TXT

(Submitter supplied) Bi-allelic hypomorphic mutations in DNMT3B disrupt DNA methyltransferase activity and lead to Immunodeficiency, Centromeric instability, Facial anomalies syndrome, type 1 (ICF1). While several ICF1 phenotypes have been linked to abnormally hypomethylated repetitive regions, the unique genomic regions responsible for the remaining disease phenotypes remain largely uncharacterized. Here we explored two ICF1 patient-induced pluripotent stem cells (iPSCs) and their CRISPR-Cas9 corrected clones to determine whether DNMT3B correction can globally overcome DNA methylation defects and related changes in the epigenome. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL16791 GPL24676

19 Samples

Download data: TXT

(Submitter supplied) Bi-allelic hypomorphic mutations in DNMT3B disrupt DNA methyltransferase activity and lead to Immunodeficiency, Centromeric instability, Facial anomalies syndrome, type 1 (ICF1). While several ICF1 phenotypes have been linked to abnormally hypomethylated repetitive regions, the unique genomic regions responsible for the remaining disease phenotypes remain largely uncharacterized. Here we explored two ICF1 patient-induced pluripotent stem cells (iPSCs) and their CRISPR-Cas9 corrected clones to determine whether DNMT3B correction can globally overcome DNA methylation defects and related changes in the epigenome. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

74 Samples

Download data: BED

(Submitter supplied) DNA methylation has suppressive effects on gene transcription and it is involved in a variety of physiologic processes, including development and cancer. As we and others demonstrated, Dnmt3b is a tumor suppressor in oncogene-driven lymphoid and myeloid malignancies in mice. Due to numerous activities such as methylation-dependent and independent repression and accessory functions, it is difficult to pinpoint physiological processes solely dependent on catalytic activity of Dnmt3b. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL24247 GPL24676

31 Samples

Download data: BIGWIG, TXT