Discovery of a regulatory polymorphism in the bovine PICALM gene associated with αS1-casein concentration in milk

This variant is located in an open chromatin region, suggesting that it could be a regulatory variant. Using a bioinformatic script, we predicted that the alternative C allele induces the loss of the yin yang 1 (YY1) transcription factor binding site. YY1 is known to play a fundamental role in biological processes and exerts its effects by activating or repressing transcription. YY1 is expressed in most bovine tissues, including mammary gland tissue. In addition, rs381381526 is located in an ATAC peak found in the mammary gland. All these results suggest that rs381381526 is potentially a regulatory variant that could alter the expression of PICALM.

To study the regulatory effects of the rs381381526 variant, we constructed and tested two vectors containing the PICALM promoter with each of the two alleles using the luciferase reporter system and the MAC-T bovine mammary epithelial cell line. Luciferase assays showed that the construct carrying the C allele induced an increase in luciferase activity of more than 20% compared to the construct carrying the G allele. These results suggest that rs381381526 is a cis-regulatory variant and that the C allele could lead to increased expression of PICALM mRNA.

Further work is needed to demonstrate that this is a causal polymorphism directly responsible for its association with αS1-casein concentration in milk.

This work was carried out as part of the European H2020 BovReg project. (https://bovreg.eu/).

Contact Scientific contact : Dominique Rocha (Dominique.rocha@inrae.fr)

Reference :
Mélissa Poncet, Maureen Féménia, Maxime Ben-Braiek, Mathieu Charles, Nathalie Duprat, Katarzyna Chałaśkiewicz, Arnaud Boulling, Hiroaki Taniguchi, Véronique Blanquet, Dominique Rocha (2025). Discovery of a regulatory polymorphism in the bovine PICALM gene associated with milk αS1-casein concentration. Animal Genetics doi.org/10.1111/age.70036