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DNA methylation changes in Down syndrome derived neural iPSCs uncover co-dysregulation of ZNF and HOX3 families of transcription factors
- Source :
- Clinical Epigenetics
- Publication Year :
- 2020
- Publisher :
- Uppsala universitet, Medicinsk genetik och genomik, 2020.
-
Abstract
- Background Down syndrome (DS) is characterized by neurodevelopmental abnormalities caused by partial or complete trisomy of human chromosome 21 (T21). Analysis of Down syndrome brain specimens has shown global epigenetic and transcriptional changes but their interplay during early neurogenesis remains largely unknown. We differentiated induced pluripotent stem cells (iPSCs) established from two DS patients with complete T21 and matched euploid donors into two distinct neural stages corresponding to early- and mid-gestational ages. Results Using the Illumina Infinium 450K array, we assessed the DNA methylation pattern of known CpG regions and promoters across the genome in trisomic neural iPSC derivatives, and we identified a total of 500 stably and differentially methylated CpGs that were annotated to CpG islands of 151 genes. The genes were enriched within the DNA binding category, uncovering 37 factors of importance for transcriptional regulation and chromatin structure. In particular, we observed regional epigenetic changes of the transcription factor genes ZNF69, ZNF700 and ZNF763 as well as the HOXA3, HOXB3 and HOXD3 genes. A similar clustering of differential methylation was found in the CpG islands of the HIST1 genes suggesting effects on chromatin remodeling. Conclusions The study shows that early established differential methylation in neural iPSC derivatives with T21 are associated with a set of genes relevant for DS brain development, providing a novel framework for further studies on epigenetic changes and transcriptional dysregulation during T21 neurogenesis.
- Subjects :
- Adult
Epigenomics
Male
induced pluripotent stem cells
Neurogenesis
Down syndrome
Induced Pluripotent Stem Cells
Trisomy
Biology
Chromatin remodeling
Fetus
Pregnancy
transcription factors
Transcription factors
Genetics
Humans
Epigenetics
Promoter Regions, Genetic
Induced pluripotent stem cell
Molecular Biology
Genetics (clinical)
Medicinsk genetik
Research
Brain
High-Throughput Nucleotide Sequencing
Promoter
DNA Methylation
Chromatin Assembly and Disassembly
Chromatin
neurogenesis
Gene Expression Regulation
CpG site
Neurodevelopmental Disorders
DNA methylation
gene expression
CpG Islands
Female
Gene expression
Chromosome 21
DNA-methylation
Medical Genetics
Developmental Biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Clinical Epigenetics
- Accession number :
- edsair.doi.dedup.....7fef917a3c433ae0df893b1a8b53b5a4