Peg3, also known as Paternally expressed gene 3, is an imprinted gene encoding a DNA-binding protein that functions as a transcriptional repressor [1,2,4,5]. It is located within the Peg3 imprinted domain along with several other imprinted genes, sharing features like co-regulation through cis-regulatory elements and playing roles in controlling fetal growth rates and maternal-caring behaviors [2].

Studies using gene knockout models have revealed multiple functions of Peg3. In lipid metabolism, Peg3 can transcriptionally repress Acly, one of its downstream genes, and also shows a sex-biased response in regulating the expression of genes like Acly, Fasn, and Idh1 involved in adipogenesis [1]. In renal clear cell carcinoma, epigenetic inactivation of Peg3 promotes tumor progression, as overexpression of Peg3 inhibits cell proliferation and colony formation, while its removal has the opposite effect [3]. In the context of the MSL complex, complete removal of PEG3 leads to up-regulation of Msl1 and Msl3, increasing global H4K16ac levels, suggesting that Peg3 controls downstream genes through the MSL complex [4]. In addition, Peg3 knockout in nursing female mice results in increased expression of Oxtr, indicating its role as a transcriptional regulator of Oxtr in the milk letdown process [6].

In conclusion, Peg3 plays crucial roles in various biological processes such as lipid metabolism, tumor suppression, and regulation of histone modification-related pathways. The use of gene knockout mouse models has been instrumental in uncovering these functions, highlighting its significance in understanding diseases like renal clear cell carcinoma and metabolic disorders [1,3,4,6].

References:

1. Ghimire, Subash, Kim, Joomyeong. 2021. PEG3 controls lipogenesis through ACLY. In PloS one, 16, e0252354. doi:10.1371/journal.pone.0252354. https://pubmed.ncbi.nlm.nih.gov/34048454/

2. He, Hongzhi, Kim, Joomyeong. 2014. Regulation and function of the peg3 imprinted domain. In Genomics & informatics, 12, 105-13. doi:10.5808/GI.2014.12.3.105. https://pubmed.ncbi.nlm.nih.gov/25317109/

3. Qiu, Teng, Ding, Yuanyuan, Qin, Jingting, Ji, Jing, Li, Guanchu. 2023. Epigenetic reactivation of PEG3 by EZH2 inhibitors suppresses renal clear cell carcinoma progress. In Cellular signalling, 107, 110662. doi:10.1016/j.cellsig.2023.110662. https://pubmed.ncbi.nlm.nih.gov/37001595/

4. Ye, An, Kim, Hana, Kim, Joomyeong. 2017. PEG3 control on the mammalian MSL complex. In PloS one, 12, e0178363. doi:10.1371/journal.pone.0178363. https://pubmed.ncbi.nlm.nih.gov/28609438/

5. He, Hongzhi, Ye, An, Kim, Hana, Kim, Joomyeong. 2016. PEG3 Interacts with KAP1 through KRAB-A. In PloS one, 11, e0167541. doi:10.1371/journal.pone.0167541. https://pubmed.ncbi.nlm.nih.gov/27898713/

6. Frey, Wesley D, Sharma, Kaustubh, Cain, Terri L, Teruyama, Ryoichi, Kim, Joomyeong. 2018. Oxytocin receptor is regulated by Peg3. In PloS one, 13, e0202476. doi:10.1371/journal.pone.0202476. https://pubmed.ncbi.nlm.nih.gov/30106994/