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. 2021 May 21;12(6):790.
doi: 10.3390/genes12060790.

Methylation of Estrogen Receptor 1 Gene in the Paraspinal Muscles of Girls with Idiopathic Scoliosis and Its Association with Disease Severity

Piotr Janusz  1 , Małgorzata Chmielewska  2 , Mirosław Andrusiewicz  2 , Małgorzata Kotwicka  2 , Tomasz Kotwicki  1
Affiliations

Methylation of Estrogen Receptor 1 Gene in the Paraspinal Muscles of Girls with Idiopathic Scoliosis and Its Association with Disease Severity

Piotr Janusz et al. Genes (Basel). .

Abstract

Idiopathic scoliosis (IS) is a multifactorial disease with epigenetic modifications. Tissue dependent and differentially methylated regions (T-DMRs) may regulate tissue-specific expression of the estrogen receptor 1 gene (ESR1). This study aimed to analyze methylation levels within T-DMR1 and T-DMR2 and its concatenation with ESR1 expression of IS patients. The study involved 87 tissue samples (deep paravertebral muscles, both on the convex and the concave side of the curve, and from back superficial muscles) from 29 girls who underwent an operation due to IS. Patient subgroups were analyzed according to Cobb angle ≤70° vs. >70°. Methylation was significantly higher in the superficial muscles than in deep paravertebral muscles in half of the T-DMR1 CpGs and all T-DMR2 CpGs. The methylation level correlated with ESR1 expression level on the concave, but not convex, side of the curvature in a majority of the T-DMR2 CpGs. The T-DMR2 methylation level in the deep paravertebral muscles on the curvature's concave side was significantly lower in patients with a Cobb angle ≤70° in four CpGs. DNA methylation of the T-DMRs is specific to muscle tissue location and may be related to ESR1 expression regulation. Additionally, the difference in T-DMR2 methylation may be associated with IS severity.

Keywords: DNA methylation; ESR1; adolescent idiopathic scoliosis; estrogen receptor 1; idiopathic; pyrosequencing; scoliosis; scoliosis progression; spinal curvatures.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
ESR1 promoters (A-D) and T-DMR1, and T-DMR2 regions localization with respect to transcription start site (TSS) and translation start codon (ATG). EGR1 indicates transcription factor binding sites. Adapted from [34].
Figure 2
Figure 2
Dot plot of ESR1 T-DMR1 and T-DMR2 regions methylation pattern of individual patients.
Figure 3
Figure 3
DNA methylation level within ESR1 T-DMR1 region in deep paravertebral muscles and superficial muscles; ** p < 0.01, *** p < 0.001.
Figure 4
Figure 4
DNA methylation level within ESR1 T-DMR2 region in deep paravertebral muscles and superficial muscles; * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 5
Figure 5
Correlation between ESR1 expression and methylation level within T-DMR1 and T-DMR2 regions in deep paravertebral muscles and superficial muscles. R—Spearman rank correlation coefficient.
Figure 6
Figure 6
DNA methylation level within ESR1 T-DMR2 region in deep paravertebral muscles and superficial muscles in patients with Cobb angles ≤70° and >70°; * p < 0.05, ** p < 0.01.
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