DNA Methylation Dynamics of Long Noncoding RNA During Human Fetal Development

Abstract

Aim: To determine whether the promoters of long noncoding RNAs (lncRNAs) undergo dynamic changes in DNA methylation during fetal development. Methods: ANOVA and the tissue specificity index were used to identify and validate tissue-specific methylation sites. Age-associated DNA methylation signatures were identified by applying the elastic net method. Results: The lncRNA methylome landscape was characterized in four types of fetal tissue and at three gestational time points, and specific characteristics relative to the tissue of origin and developmental age were identified. Higher levels of lncRNA methylation might be involved in tissue differentiation. LncRNAs harboring age-associated methylation signatures may participate in the fetal developmental process. Conclusion: This study provides novel insights into the role of lncRNA methylomes in fetal tissue specification and development.

Lay abstract

The addition of a methyl group to DNA is known as DNA methylation and has a large impact on early embryonic development. The role of specific DNA methylation sites located in the promoter region of long noncoding RNA (lncRNA) during human fetal development is not fully understood. The DNA methylation of lncRNA promoters was investigated in four types of tissue and at three gestational time points. They display tissue-specific characteristics that change over time. Tissue-specific methylation sites have higher levels of methylation, suggesting they might play a role in tissue differentiation. The lncRNAs that show loss or gain of methylation over time may participate in the fetal developmental process. This study describes the DNA methylation status of lncRNA promoters and elucidates their potential role in fetal development.

Keywords::

• DNA methylation
• dynamic
• fetal development
• lncRNA
• specific

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0159

Author contributions

S Ning, S Qu, X Li and Y Fu designed the study and performed analysis. S Ning and X Li supervised research and provided critical advice on the study. X Li and Y Fu wrote the manuscript. Y Gao, S Shang, S Guo and H Zhou collected data and developed the methodology. All authors read and approved the final manuscript.

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (32070672), Postdoctoral Scientific Research Developmental Fund, and Yu Weihan Outstanding Youth Training Fund of Harbin Medical University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing support was provided by International Science Editing and was funded by Yu Weihan Outstanding Youth Training Fund of Harbin Medical University.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (32070672), Postdoctoral Scientific Research Developmental Fund, and Yu Weihan Outstanding Youth Training Fund of Harbin Medical University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing support was provided by International Science Editing and was funded by Yu Weihan Outstanding Youth Training Fund of Harbin Medical University.