Methylation profiling

Dataset Information

0

Trans-effects of chromosome aneuploidies on DNA methylation patterns: DNA methylation analysis of Down syndrome in human brain tissues and cells


ABSTRACT: Background: Trisomy 21 causes Down syndrome (DS), but the mechanisms by which the extra chromosome leads to deficient intellectual and immune function are not well understood. Results: Here, we profile CpG methylation in DS and control cerebral and cerebellar cortex of adults and cerebrum of fetuses. We purify neuronal and non-neuronal nuclei and T-lymphocytes and find biologically relevant genes with DS-specific methylation (DS-DM) in brain cells. Some genes show brain-specific DS-DM, while others show stronger DS-DM in T cells. Both 5-methyl-cytosine and 5-hydroxy-methyl-cytosine contribute to the DS-DM. Thirty percent of genes with DS-DM in adult brain cells also show DS-DM in fetal brains, indicating early onset of these epigenetic changes, and we find early maturation of methylation patterns in DS brain and lymphocytes. Some, but not all, of the DS-DM genes show differential expression. DS-DM preferentially affected CpGs in or near specific transcription factor binding sites, implicating a mechanism involving altered transcription factor binding. Methyl-seq of brain DNA from mouse models with sub-chromosomal duplications mimicking DS reveals partial but significant overlaps with human DS-DM and shows that multiple chromosome 21 genes contribute to the downstream epigenetic effects. Conclusions: These data point to novel biological mechanisms in DS and have general implications for trans effects of chromosomal duplications and aneuploidies on epigenetic patterning.

ORGANISM(S): Homo sapiens

PROVIDER: GSE74486 | GEO | 2015/10/30

SECONDARY ACCESSION(S): PRJNA300574

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2015-10-30 | E-GEOD-74505 | biostudies-arrayexpress
2015-10-30 | GSE74505 | GEO
2015-10-30 | E-GEOD-74486 | biostudies-arrayexpress
2018-04-01 | GSE111621 | GEO
2022-02-24 | PXD003401 | Pride
2013-04-07 | E-GEOD-44304 | biostudies-arrayexpress
2021-12-30 | PXD028148 | Pride
2018-01-19 | GSE95013 | GEO
2018-05-09 | GSE85251 | GEO
2013-08-19 | E-GEOD-46167 | biostudies-arrayexpress