Genetic and Epigenetic Regulation of the FLO Gene Family Generates Cell-surface Variation in Yeast

The FLO gene family of Saccharomyces cerevisiae includes an expressed gene, FLO11, and a set of silent, telomere-adjacent FLO genes. This gene family encodes cell-wall glycoproteins that regulate cell-cell and cell-surface adhesion. Epigenetic silencing of FLO11 regulates a key developmental switch: when FLO11 is expressed, diploid cells form pseudohyphal filaments; when FLO11 is silent, the cells grow in yeast form. The epigenetic state of FLO11 is heritable for many generations and regulated by the histone deacetylase (HDAC) Hda1p. The silent FLO10 gene is activated by high-frequency loss-of-function mutations at either IRA1 or IRA2. FLO10 is regulated by the same transcription factors that control FLO11: Sfl1p and Flo8p, but is silenced by a distinct set of HDACs: Hst1p and Hst2p. These sources of epigenetic and genetic variation explain the observed heterogeneity of cell-surface protein expression within a population of cells derived from a single clone.