Abstract
Peg3 (Paternally expressed gene 3) is an imprinted gene encoding a DNA-binding protein that is a well-known transcriptional repressor. Previous studies have shown that the mutant phenotypes of Peg3 are associated with the over-expression of genes involved in lipid metabolism. In the current study, we investigated four potential downstream genes of Peg3, which were identified through ChIP-seq data: Acly, Fasn, Idh1, and Hmgcr. In vivo binding of PEG3 to the promoter region of these key genes involved in lipogenesis was subsequently confirmed through individual ChIP experiments. We observed the opposite response of Acly expression levels against the variable gene dosages of Peg3, involving 0x, 1x, and 2x Peg3. This suggests the transcriptional repressor role of Peg3 in the expression levels of Acly. Another set of analyses showed a sex-biased response in the expression levels of Acly, Fasn, and Idh1 against 0x Peg3 with higher levels in female and lower levels in male mammary glands. These results overall highlight that Peg3 may be involved in regulating the expression levels of several key genes in adipogenesis.
Highlights
Epigenetics is an external modification to DNA that affects gene expression without altering the DNA sequence [1]
We characterized four downstream genes of Paternally expressed gene 3 (Peg3) involved in lipogenesis: Acly, Idh1, Hmgcr, and Fasn, which were identified through analyzing previous ChIP-seq data [34]
This study suggests that Peg3 is involved in regulating the expression levels of key genes in adipogenesis
Summary
Epigenetics is an external modification to DNA that affects gene expression without altering the DNA sequence [1]. Genomic imprinting is an epigenetic phenomenon in which one allele is expressed while the other one is silenced, depending on its parental origin. This unusual expression pattern is achieved through DNA methylation and histone modification [2, 3]. Around 200 imprinted genes are predicted to be present in eutherian mammals and believed to be involved in fetal development and animal behaviors [4]. These imprinted genes are typically clustered in specific chromosomal regions [5]. Imprinted genes are generally regulated through shared cis-regulatory elements, which are referred to as imprinting control regions (ICRs) [6]
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