Research Projects

This project aims to understand the link between chromatin state and transcriptional circuitry in the human fungal pathogen Candida albicans. The project will combine molecular genetics and biochemistry experiments with mutational analyses in C. albicans. The C. albicans genome encodes two paralogous histone H2B-like histone fold domain (HFD) containing TAF12 proteins, TAF12 and TAF12L, which associate with the general transcription factor TFIID and the histone modifying SAGA complex in vivo. In vitro, TAF12 and TAF12L form heterodimers with H2A-like HFD containing TAF4 and Ada1. The mechanism for this specificity in vivo is unclear. The project will focus on two specific objectives: addressing the logic of macromolecular assembly of large TFIID and SAGA transcriptional regulatory protein complexes, and addressing the cross-talk between the HAT enzymes Gcn5 and Esa1, which acetylate H3 Lys9 and H4 Lys5, respectively. The researchers hypothesize that filamentation transcriptional regulators recruit SAGA to acetylate promoter nucleosomes, and the NuA4 complex then acetylate H4. The researchers will employ catalytically dead HAT mutants and test the recruitment of SAGA and NuA4 complexes/activities in vivo. These studies will provide a molecular framework for gene regulation in C. albicans and provide a better understanding of cross-talks between various histone modifications that are hallmarks of chromatin control of gene regulation in yeast to humans.