Release from Polycomb-mediated repression at the chromatin: Structure-function study of a critical switch at plant developmental genes – ChromSwitch

Plants sessile habit constrains their development and growth to the environment. This requires high adaptability of gene networks that build plant architecture and drive continuous organogenesis. Precise spatio-temporal regulation of developmental genes involves a ballet of epigenetic repressors and activators at the chromatin. Despite the importance of this regulatory level, the molecular mechanisms underlying the switch from repression to activation are poorly understood. The ChromSwitch project aims to provide novel insights into the antagonistic action of epigenetic regulators, using the ULTRAPETALA1 (ULT1) function as a paradigm. The transcriptional activator ULT1 antagonizes the Polycomb Repressive Complex 2 (PRC2), whose appropriate release is essential for establishing a correct body plan. While PRC2 deposits the trimethyl repressive mark on Histone 3 Lysine 27 (H3K27me3) at developmental genes, ULT1 causes the mark to decrease at these genes, for flowering transition and flower morphogenesis. In our preliminary work, we found that ULT1 physically interacts with PRC2 methyl transferases. We also obtained first structural insights into ULT1 and showed that it interacts both with modified histones and with DNA. Specific objectives of this proposal are the structure-function characterizations of ULT1 interaction (i) with histone H3 and DNA, in order to understand how it targets genes, and (ii) with PRC2, in order to decrypt its opposing mechanism to H3K27me3 deposition. Using an integrative approach including in vitro biochemistry and biophysics and in vivo molecular and genetics analyses, ChromSwitch will reveal and characterise a novel epigenetic mechanism for regulation of development and cell fate. It should impact fundamental science in the plant and animal biology fields, with possible further developments in the agricultural sector.