Title: Computational promoter analysis of ovine lipogenic genes reveals insulin as a major factor potentially responsible for their synergistic transcription

Authors: Kristian Christos Kailis; Iosif Bizelis; Panagiota Koutsouli; George P. Laliotis

Addresses: Laboratory of Animal Breeding and Husbandry, Department of Animal Science, Agricultural University of Athens, 75 Iera Odos, GR11855, Athens, Greece ' Laboratory of Animal Breeding and Husbandry, Department of Animal Science, Agricultural University of Athens, 75 Iera Odos, GR11855, Athens, Greece ' Laboratory of Animal Breeding and Husbandry, Department of Animal Science, Agricultural University of Athens, 75 Iera Odos, GR11855, Athens, Greece ' Laboratory of Animal Breeding and Husbandry, Department of Animal Science, Agricultural University of Athens, 75 Iera Odos, GR11855, Athens, Greece

Abstract: De novo lipogenesis (DNL) is an important metabolic pathway in ruminants and non-ruminants. In sheep, cytosolic dehydrogenases of glucose-6-phosphate (G6PD), 6-phosphorogluconic (6PGD), isocitric (IDH1) and malic acid (ME1) contribute to the required NADPH for DNL. A synergic action of these enzymes has been reported, but the common regulatory mechanism is unknown. The study aimed to identify: 1) the promoter region of these genes; 2) any potential regions for transcription factor binding; 3) potential common transcription factors; 4) differences between ruminant and non-ruminant counterparts. Results showed structural differences in the promoter region among species. Ten transcription factors were found to be commonly present, including USF1 and HNF-3β, which are involved in lipogenesis and are considered as insulin-dependent. Therefore, the 'insulin-USF-HNF' triptych may have an impact on the synergistic action of the studied genes since both USF and HNF expression are insulin-dependent. Accordingly, any stimulus that alters insulin could alter the expression of the studied genes through USF and HNF accumulation. Overall, this study provides valuable insights into the transcription process of these genes and the lipogenesis pathway in sheep.

Keywords: lipogenesis; fatty acids; ruminants; sheep; metabolism; NADPH; genomics; transcription factors; binding sites; lipidomics; G6PD; 6PGD; IDH1; ME1.

DOI: 10.1504/IJBRA.2024.141380

International Journal of Bioinformatics Research and Applications, 2024 Vol.20 No.4, pp.370 - 398

Received: 28 Jul 2023
Accepted: 04 Dec 2023
Published online: 10 Sep 2024 *

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