AUTHOR=Jiang Keren , Ma Zheng , Wang Zhang , Li Hong , Wang Yanbin , Tian Yadong , Li Donghua , Liu Xiaojun 

TITLE=Evolution, Expression Profile, Regulatory Mechanism, and Functional Verification of EBP-Like Gene in Cholesterol Biosynthetic Process in Chickens (Gallus Gallus)

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.587546

DOI=10.3389/fgene.2020.587546

ISSN=1664-8021

ABSTRACT=<p>The emopamil binding protein (EBP) is an important enzyme participating in the final steps of cholesterol biosynthesis in mammals. A predictive gene <italic>EBP-like</italic>, which encodes the protein with a high identity to human EBP, was found in chicken genome. No regulatory mechanisms and biological functions of <italic>EBP-like</italic> have been characterized in chickens. In the present study, the coding sequence of <italic>EBP-like</italic> was cloned, the phylogenetic trees of EBP/EBP-like were constructed and the genomic synteny of <italic>EBP-like</italic> was analyzed. The regulatory mechanism of <italic>EBP-like</italic> were explored with <italic>in vivo</italic> and <italic>in vitro</italic> experiments. The biological functions of <italic>EBP-like</italic> in liver cholesterol biosynthetic were examined by using gain- or loss-of-function strategies. The results showed that chicken <italic>EBP-like</italic> gene was originated from a common ancestral with Japanese quail <italic>EBP</italic> gene, and was relatively conservative with <italic>EBP</italic> gene among different species. The <italic>EBP-like</italic> gene was highly expressed in liver, its expression level was significantly increased in peak-laying stage, and was upregulated by estrogen. Inhibition of the <italic>EBP-like</italic> mRNA expression could restrain the expressions of <italic>EBP-like</italic> downstream genes (<italic>SC5D</italic>, <italic>DHCR24</italic>, and <italic>DHCR7</italic>) in the cholesterol synthetic pathway, therefore downregulate the liver intracellular T-CHO level. In conclusion, as substitute of <italic>EBP</italic> gene in chickens, <italic>EBP-like</italic> plays a vital role in the process of chicken liver cholesterol synthesis. This research provides a basis for revealing the molecular regulatory mechanism of cholesterol synthesis in birds, contributes insights into the improvement of the growth and development, laying performance and egg quality in poultry.</p>