PUBLICATION
Genomics of CpG Methylation in Developing and Developed Zebrafish
- Authors
- McGaughey, D.M., Ozel Abaan, H., Miller, R.M., Kropp, P.A., Brody, L.C.
- ID
- ZDB-PUB-140513-298
- Date
- 2014
- Source
- G3 (Bethesda) 4(5): 861-9 (Journal)
- Registered Authors
- Keywords
- Development, Epigenetics, Methylation, One-carbon metabolism, Zebrafish
- Datasets
- GEO:GSE52110
- MeSH Terms
-
- Alternative Splicing
- Animals
- Cluster Analysis
- Computational Biology
- CpG Islands*
- DNA Methylation*/drug effects
- Epigenesis, Genetic
- Exons
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Developmental/drug effects
- Genomics*
- Humans
- Long Interspersed Nucleotide Elements
- Male
- Methotrexate/pharmacology
- Organ Specificity/genetics
- Promoter Regions, Genetic
- Short Interspersed Nucleotide Elements
- Transcriptome
- Zebrafish/embryology
- Zebrafish/genetics*
- PubMed
- 24657902 Full text @ G3 (Bethesda)
Citation
McGaughey, D.M., Ozel Abaan, H., Miller, R.M., Kropp, P.A., Brody, L.C. (2014) Genomics of CpG Methylation in Developing and Developed Zebrafish. G3 (Bethesda). 4(5):861-9.
Abstract
DNA methylation is a dynamic process through which specific chromatin modifications can be stably transmitted from parent to daughter cells. A large body of work has suggested that DNA methylation influences gene expression by silencing gene promoters. However, these conclusions were drawn from data focused mostly on promoter regions. With regards to the entire genome, it is unclear how methylation and gene transcription patterns are related during vertebrate development. To identify the genome-wide distribution of CpG methylation we created series of high-resolution methylome maps of Danio rerio embryos during development and in mature, differentiated tissues. We find that embryonic and terminal tissues have unique methylation signatures in CpG islands and repetitive sequences. Fully differentiated tissues have increased CpG and LTR methylation and decreased SINE methylation relative to embryonic tissues. Unsupervised clustering analyses reveal that the embryonic and terminal tissues can be classified solely by their methylation patterning. Novel analyses also identify a previously undescribed genome-wide exon methylation signature. We also compared whole genome methylation with genome-wide mRNA expression levels using publicly available RNA-seq datasets. These comparisons revealed previously unrecognized relationships between gene-expression, alternative splicing and exon methylation. Surprisingly, we find that exonic methylation is a better predictor of mRNA expression level than promoter methylation. We also found that transcriptionally skipped exons have significantly less methylation than retained exons. Our integrative analyses reveal highly complex interplay between gene expression, alternative splicing, development, and methylation patterning in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping