TY  - JOUR
A1  - Schneider, Eberhard
A1  - Dittrich, Marcus
A1  - Böck, Julia
A1  - Nanda, Indrajit
A1  - Müller, Tobias
A1  - Seidmann, Larissa
A1  - Tralau, Tim
A1  - Galetzka, Danuta
A1  - El Hajj, Nady
A1  - Haaf, Thomas
T1  - CpG sites with continuously increasing or decreasing methylation from early to late human fetal brain development
JF  - Gene
N2  - Normal human brain development is dependent on highly dynamic epigenetic processes for spatial and temporal gene regulation. Recent work identified wide-spread changes in DNA methylation during fetal brain development. We profiled CpG methylation in frontal cortex of 27 fetuses from gestational weeks 12-42, using Illumina 450K methylation arrays. Sites showing genome-wide significant correlation with gestational age were compared to a publicly available data set from gestational weeks 3-26. Altogether, we identified 2016 matching developmentally regulated differentially methylated positions (m-dDMPs): 1767 m-dDMPs were hypermethylated and 1149 hypomethylated during fetal development. M-dDMPs are underrepresented in CpG islands and gene promoters, and enriched in gene bodies. They appear to cluster in certain chromosome regions. M-dDMPs are significantly enriched in autism-associated genes and CpGs. Our results promote the idea that reduced methylation dynamics during fetal brain development may predispose to autism. In addition, m-dDMPs are enriched in genes with human-specific brain expression patterns and/or histone modifications. Collectively, we defined a subset of dDMPs exhibiting constant methylation changes from early to late pregnancy. The same epigenetic mechanisms involving methylation changes in cis-regulatory regions may have been adopted for human brain evolution and ontogeny.
KW  - Autism spectrum disorders
KW  - DNA methylation
KW  - Genome
KW  - Autism
KW  - Frontal cortex
KW  - Human prefrontal cortex
KW  - Gene-expression
KW  - Schizophrenia
KW  - Patterns
KW  - Transcription
KW  - Epigenetics
KW  - Environment
KW  - Fetal brain development
KW  - DNA methylation dynamics
KW  - Methylome
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186936
VL  - 592
IS  - 1
ER  - 
TY  - JOUR
A1  - Matos, Isa
A1  - Machado, Miguel P.
A1  - Schartl, Manfred
A1  - Coelho, Maria Manuela
T1  - Allele-specific expression variation at different ploidy levels in Squalius alburnoides
JF  - Scientific Reports
N2  - Allopolyploid plants are long known to be subject to a homoeolog expression bias of varying degree. The same phenomenon was only much later suspected to occur also in animals based on studies of single selected genes in an allopolyploid vertebrate, the Iberian fish Squalius alburnoides. Consequently, this species became a good model for understanding the evolution of gene expression regulation in polyploid vertebrates. Here, we analyzed for the first time genome-wide allele-specific expression data from diploid and triploid hybrids of S. alburnoides and compared homoeolog expression profiles of adult livers and of juveniles. Co-expression of alleles from both parental genomic types was observed for the majority of genes, but with marked homoeolog expression bias, suggesting homoeolog specific reshaping of expression level patterns in hybrids. Complete silencing of one allele was also observed irrespective of ploidy level, but not transcriptome wide as previously speculated. Instead, it was found only in a restricted number of genes, particularly ones with functions related to mitochondria and ribosomes. This leads us to hypothesize that allelic silencing may be a way to overcome intergenomic gene expression interaction conflicts, and that homoeolog expression bias may be an important mechanism in the achievement of sustainable genomic interactions, mandatory to the success of allopolyploid systems, as in S. alburnoides.
KW  - Gene expression analysis
KW  - Transcription
KW  - Transcriptomic
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200910
VL  - 9
ER  -