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Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries

  1. Sebastian Ocklenburg  Is a corresponding author
  2. Judith Schmitz
  3. Zahra Moinfar
  4. Dirk Moser
  5. Rena Klose
  6. Stephanie Lor
  7. Georg Kunz
  8. Martin Tegenthoff
  9. Pedro Faustmann
  10. Clyde Francks
  11. Jörg T Epplen
  12. Robert Kumsta
  13. Onur Güntürkün
  1. Ruhr University Bochum, Germany
  2. St. Johannes Hospital, Germany
  3. University Hospital Bergmannsheil, Germany
  4. Max Planck Institute for Psycholinguistics, Netherlands
  5. Radboud University, Netherlands
  6. Wallenberg Research Centre at Stellenbosch University, South Africa
Research Article
Cite this article as: eLife 2017;6:e22784 doi: 10.7554/eLife.22784
3 figures and 1 additional file

Figures

Gene expression asymmetries in human fetal spinal cord at 8, 10 and 12 weeks PC.

X-axis shows the extent of asymmetry measured in log2(fold change) between right and left spinal cord samples. Blue bars show leftward asymmetrically expressed genes, red bars show rightward asymmetrically expressed genes. For 8 weeks PC, the top 25 genes with highest rightward/leftward gene expression asymmetries are depicted. For 10 and 12 weeks PC, all genes with a log2(fold change) > 1.5 are shown. The source files of asymmetrically expressed genes per developmental stage with corresponding fold change values are available in Figure 1—source data 1.

https://doi.org/10.7554/eLife.22784.002
Figure 1—source data 1

Asymmetrically expressed genes per week.

https://doi.org/10.7554/eLife.22784.003
Functional genes and gene groups.

(A) Gene expression asymmetries for previously published candidate genes for handedness and functional lateralization. Asterisks indicate biologically relevant gene expression asymmetry with a log2(fold change) > 1.5. (B) Number of significant Gene Ontology (GO) groups for the three main categories ‘biological processes’, 'molecular function' and 'cellular component' for weeks 8, 10 and 12 PC. (C) Main GO groups for 8 and 10 weeks PC with p-value and number of involved genes for the left and right spinal cord. The source files of all enriched GO groups are available in Figure 2—source data 1.

https://doi.org/10.7554/eLife.22784.004
Figure 2—source data 1

Enriched GO groups per week and side of the spinal cord.

https://doi.org/10.7554/eLife.22784.005
Epigenetic regulation of gene expression asymmetries in human fetal spinal cord.

(A) Asymmetrically expressed miRNA transcripts at 8, 10 and 12 weeks PC. The extent of expression asymmetries is measured in log2(fold change). Red bars show rightward asymmetrically expressed microRNA transcripts, blue bars show leftward asymmetrically expressed miRNA transcripts. (B) Number of CpG sites showing differential DNA methylation per chromosome, compared between the left and right spinal cord for 8 and 10 weeks PC. Depicted are only CpG sites with methylation asymmetries in both samples. Red bars represent the number of CpG sites that showed significantly higher DNA methylation on the right side, blue bars show the number of CpG sites that showed significantly more DNA methylation on the left side. (C) Percentage of differential DNA methylation in leftward (blue) and rightward (red) asymmetrically methylated CpG sites as a function of p-value. (D) Percentage of gene expression asymmetries on each chromosome at 8 weeks PC that can be explained by regulation via asymmetrically expressed miRNAs or asymmetric DNA methylation of CpG sites within and 1500 nucleotides upstream of the expressed genes. The source files of asymmetrically expressed miRNAs, asymmetrically expressed targets of miRNAs, enriched KEGG pathways and differentially methylated CpG sites are available in Figure 3—source data 1, Figure 3—source data 2, Figure 3—source data 3, and Figure 3—source data 4 respectively.

https://doi.org/10.7554/eLife.22784.006
Figure 3—source data 1

Asymmetrically expressed miRNAs per week.

https://doi.org/10.7554/eLife.22784.007
Figure 3—source data 2

Asymmetrically expressed RNA targets of asymmetrically expressed miRNAs per week.

https://doi.org/10.7554/eLife.22784.008
Figure 3—source data 3

Enriched KEGG pathways per week and side of the spinal cord.

https://doi.org/10.7554/eLife.22784.009
Figure 3—source data 4

Asymmetrically methylated CpG sites per week and side of the spinal cord.

https://doi.org/10.7554/eLife.22784.010

Additional files

Supplementary file 1

(A) Description of tissue samples. (B) RNA quality measurements. (C) DNA quality measurements. (D) RNA read statistics. (E) DNA read statistics. (F) Methylation report. (G) Top 25 asymmetrically expressed genes per sample.

https://doi.org/10.7554/eLife.22784.011

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