Lopes lab discovers novel regulation of model genes in yeast

Lopes lab discovers novel regulation of model genes in yeast

The Lopes lab recently reported novel transcription regulation of two genes, INO1 and PHO5, which are longstanding models for eukaryotic gene regulation. It was well documented that the Ino2p/Ino4p bHLH proteins regulate INO1 transcription in response to inositol. Ameet Shetty discovered that the Cbf1p bHLH protein also regulates INO1 transcription by a mechanism that involves cooperativity with Ino2p/Ino4p and recruitment of a chromatin remodeling complex.

This study also identified two novel mechanisms for regulation in yeast. It was a generally accepted paradigm that transcription regulation in yeast is dictated by sequences within 500 basepairs upstream of genes. The INO1 study revealed that Cbf1p regulates INO1 transcription from much greater upstream distances that span the neighboring SNA3 gene. The study also revealed that Ino2p/Ino4p regulate expression of the SNA3 gene from a downstream location. This work was published in Eukaryotic Cell in 2010.

In another paper, Ying He examined regulation of the PHO5 gene. It has long been known that the Pho4p bHLH protein regulates PHO5 transcription in response to phosphate levels by a mechanism that involves nucleosome remodeling. Ying He discovered that Ino2p/Ino4p also regulate PHO5 transcription in response to inositol. Regulation by Ino2p/Ino4p was dependent on nucleosome remodeling initiated by Pho4p that exposed a binding site for Ino2p/Ino4p. This work was published in Molecular Microbiology in 2012.

Both of these studies were funded by a grant from NSF to Professor John Lopes titled: Regulation by Basic Helix-loop-helix Proteins in Yeast. The two published studies serve as examples of how much gene regulation remains to be defined even in the case of extensively studied model genes.