Abstract

Transcriptional regulatory networks play a central role in optimizing cell survival. How DNA binding domains and cis-regulatory DNA binding sequences have co-evolved to allow the expansion of transcriptional networks and how this contributes to cellular fitness remains unclear. Here we experimentally explore how the complex G1/S transcriptional network evolved in the budding yeast Saccharomyces cerevisiae by examining different chimeric transcription factor (TF) complexes. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively. The difference in size and complexity of the G1/S transcriptional network across yeast species makes it well suited to investigate how TF paralogs (SBF and MBF) and DNA binding sequences (SCB and MCB) co-evolved after gene duplication to rewire and expand the network of G1/S target genes. Our data suggests that whilst SBF is the likely ancestral regulatory complex, the ancestral DNA binding element is more MCB-like. G1/S network expansion took place by both cis- and trans- co-evolutionary changes in closely related but distinct regulatory sequences. Replacement of the endogenous SBF DNA-binding domain (DBD) with that from more distantly related fungi leads to a contraction of the SBF-regulated G1/S network in budding yeast, which also correlates with increased defects in cell growth, cell size, and proliferation.

Highlights

  • Eukaryotic cells have evolved complex transcriptional regulatory networks to ensure faithful cell division

  • The G1/S transition through the cell cycle is promoted by the periodic expression of a large set of genes regulated by a G1/S transcriptional gene network

  • Despite extensive comparative studies in different eukaryotic organisms, little is known regarding the evolution of G1/S transcriptional network expansion and how such an expansion was important for cell division and growth rate

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Summary

Introduction

Eukaryotic cells have evolved complex transcriptional regulatory networks to ensure faithful cell division. One example is the G1/S cell cycle network that includes a large set of co-regulated genes whose expression peaks at the G1-to-S transition. Activation of G1/S transcription promotes entry into S phase and the initiation of a new cell division cycle. E2F/DP is a large family of winged helix-turnhelix transcription factors that regulate G1/S target genes. In budding yeast (S. cerevisiae), the main G1/S transcription factor (TF) components, Swi, Swi and Mbp, form two heterodimer transcription factor complexes: a common Swi subunit plus one of the DNA binding proteins Swi or Mbp constitute SBF and MBF complexes, respectively (Fig 1A). The related components in fission yeast (S. pombe), the common Cdc subunits with Res and Res, forms a tetramer complex [1]

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