Transcriptional Regulation of the Genes Encoding Branched-Chain Aminotransferases in Kluyveromyces lactis and Lachancea kluyveri Is Independent of Chromatin Remodeling

Abstract

In yeasts, the Leu3 transcriptional factor regulates the expression of genes encoding enzymes of the leucine biosynthetic pathway, in which the first committed step is catalyzed by α-isopropylmalate synthase (α-IPMS). This enzyme is feedback inhibited by leucine, and its product, α-isopropylmalate (α-IPM), constitutes a Leu3 co-activator. In S. cerevisiae, the ScBAT1 and ScBAT2 genes encode branched-chain aminotransferase isozymes. ScBAT1 transcriptional activation is dependent on the α-IPM concentration and independent of chromatin organization, while that of ScBAT2 is α-IPM-independent but dependent on chromatin organization. This study aimed at understanding whether chromatin remodeling determines the transcriptional regulation of orthologous KlBAT1 and LkBAT1 genes in Kluyveromyces lactis and Lachancea kluyveri under conditions in which the branched-chain amino acids are synthesized or degraded. The results indicate that, in K. lactis, KlBAT1 expression is reduced under catabolic conditions, while in L. kluyveri, LkBAT1 displays a constitutive expression profile. The chromatin organization of KlBAT1 and LkBAT1 promoters did not change, maintaining the Leu3-binding sites free of nucleosomes. Comparison of the α-IPMS sensitivities to feedback inhibition suggested that the main determinant of transcriptional activation of the KlBAT1 and LkBAT1 genes might be the availability of the α-IPM co-activator, as reported previously for the ScBAT1 gene of S. cerevisiae.