The landscape of super-enhancer regulates remote target gene transcription through loop domains in adipose tissue of pig.

Background: A super-enhancer (SE) is a huge cluster of multiple enhancers that control the key genes for cell identity and function. The rise of advanced chromatin immunoprecipitation sequencing (ChIP-seq) technology such as Cleavage Under Targets and Tagmentation (CUT&Tag) allows more SEs to be discovered. However, SE studies in Luchuan and Duroc pigs are very rare in animal husbandry. Results: We used the CUT&Tag technique to identify 145 and 378 SEs from the adipose tissues of Luchuan and Duroc pigs, respectively. There were significant differences in the peak coverage ratio of SE peaks in the gene promoter region between the two breeds. Not only that, peak signals at the start and end point of the SE peak profile showed obvious spikes. The proximal target genes of SE were highly expressed compared with the background genes and the typical enhancer target genes. Subsequently, in conjoint analysis with high-throughput chromosome conformation capture sequencing (Hi-C seq) data, we predicted the remote regulatory genes of SE and found that their expression level was related to the distance of SE extended to the loop's anchor, but not the length of loops. According to our prediction model, SEs can maintain promoter accessibility of partial remote target genes through loop domains. Finally, a batch of SEs closely related to fat metabolism traits were obtained by performing a coalition analysis of quantitative trait loci and SE data. Conclusions: This work enabled us to obtain hundreds of SEs from Luchuan and Duroc pigs. Our model provides a new method for predicting the SE remote target genes based on loop domains, and to further explore the potential role of super-enhancer in the regulation of fat metabolism.

Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health. However, to date, no safe, effective and appropriate treatment modalities are available. In recent years, ferroptosis has emerged as a significant mode of cell death and has been found to play a key regulatory role in the development of NAFLD. In this study, we found that arbutin (ARB), a natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits the onset of ferroptosis and ameliorates high-fat diet-induced NAFLD in vivo and in vitro. Using reverse docking, we identified the demethylase fat mass and obesity-related protein (FTO) as a potential target of ARB. Subsequent mechanistic studies revealed that ARB plays a role in controlling methylation of the SLC7A11 gene through inhibition of FTO. In addition, we demonstrated that SLC7A11 could alleviate the development of NAFLD in vivo and in vitro. Our findings identify the FTO/SLC7A11 axis as a potential therapeutic target for the treatment of NAFLD. Specifically, we show that ARB alleviates NAFLD by acting on the FTO/SLC7A11 pathway to inhibit ferroptosis.

BATF relieves hepatic steatosis by inhibiting PD1 and promoting energy metabolism.

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) has become a global health threat that needs to be addressed urgently. Basic leucine zipper ATF-like transcription factor (BATF) is commonly thought to be involved in immunity, but its effect on lipid metabolism is not clear. Here, we investigated the function of BATF in hepatic lipid metabolism. BATF alleviated high-fat diet (HFD)-induced hepatic steatosis and inhibited elevated programmed cell death protein (PD)1 expression induced by HFD. A mechanistic study confirmed that BATF regulated fat accumulation by inhibiting PD1 expression and promoting energy metabolism. PD1 antibodies alleviated hepatic lipid deposition. In conclusion, we identified the regulatory role of BATF in hepatic lipid metabolism and that PD1 is a target for alleviation of NAFLD. This study provides new insights into the relationship between BATF, PD1, and NAFLD.