4.7 Article

The regulation of LncRNA GTL2 expression by DNA methylation during sheep skeletal muscle development

Journal

GENOMICS
Volume 114, Issue 5, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2022.110453

Keywords

DNA methylation; LncRNA GTL2; Skeletal muscle development; Sheep

Funding

  1. Natural Science Foun- dation of Jiangsu Province [BK20210403]
  2. Fundamental Research Funds for the Central Universities [KYQN2022027]
  3. National Nat- ural Science Foundation of China [32102520]

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DNA methylation plays a crucial role in regulating lncRNA expression during skeletal muscle development, as observed in the differential expression and methylation patterns of the lncRNA GTL2. The methylation levels of GTL2 DMRs increase with age, and 5AZA treatment enhances GTL2 expression. Moreover, dCas9-DNMT3A effectively increases the methylation level in the DMR region of GTL2 but reduces its expression level.
DNA methylation has crucial roles in regulating the expression of genes involved in skeletal muscle development. However, the DNA methylation pattern of lncRNA during sheep skeletal muscle development remains unclear. This study investigated previous WGBS and LncRNA data in skeletal muscle of sheep (fetus and adult). We then focused on LncRNA GTL2, which is differentially expressed in skeletal muscle and has multiple DMRs. We found that the expression level of GTL2 decreased with age. GTL2 DMRs methylation levels were significantly higher in adult muscle than in fetal muscle. After 5AZA treatment, GTL2 expression was significantly increased in a dose -dependent manner.The dCas9-DNMT3A-sgRNA significantly reduced the expression level of GTL2 in cells, but increased GTL2 DMR methylation levels. The above studies indicate that dCas9-DNMT3A can effectively increase the methylation level in the DMR region of GTL2, the expression level of GTL2 is regulated by DNA methylation during muscle development.

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