STRUCTURAL AND FUNCTIONAL STUDIES ON A HISTONE DEACETYLASE MEDIATED GENE SILENCING

Abstract

In Arabidopsis thaliana, HISTONE DEACETYLASE 6 (HDA6) plays a crucial role in gene silencing. To further understand the molecular mechanisms underlying HDA6-mediated gene silencing, I first analysed HDA6 structure by modelling, based on the human HISTONE DEACETYLASE 2 (HDAC2) crystal structure. This allowed me to visualize the interaction surface of HDA6 by mapping the residues directly involved in ligand interaction. I also analysed and identified several interaction partners of HDA6 via yeast two-hybrid assays and further characterised its known partners including FVE and MULTICOPY SUPRESSOR OF IRA (MSI5). Structural modelling of MSI1 and FVE was contrasted against the solved structure of p55 to shed light onto why FVE and MSI5 are partners with HDA6 within a histone deacetylase (HDAC) complex but not MSI1, which is a component of the PRC2 complex. I finally analysed the genetic interaction of HDA6 with one of its partners in gene silencing and found that these two genes act largely non-additively to silence their targets.