Although all cells contain exactly the same genetic information, they acquire different cellular fates. Cell differentiation refers to the passage of a cell from an undifferentiated “stem” state to a “mature” state. Differentiation is a morphogenetic process: it is accompanied by phenotypic changes on a cellular scale, resulting from profound modifications in gene expression. Activation and repression of gene expression result from the combined activity of transcription factors and chromatin regulatory complexes. Among the key players involved in these regulations, two groups of proteins function antagonistically: the Polycomb group (PcG) and the trithorax group (trxG). The Polycomb Repressive Complex 2 (PRC2) plays an essential role in maintaining thousands of genes in a repressed state, by depositing methylation marks on Histone 3 lysine 27 (H3K27me3). Conversely, trithorax group proteins counteract Polycomb group-mediated repression on common gene targets through various mechanisms. While PcG and trxG group proteins are increasingly well identified and characterized, the molecular mechanisms by which a gene switches its transcriptional status are still poorly understood. The overall aim of my PhD is to understand how chromatin and transcription dynamics interact and are orchestrated, by deciphering the dialogue between chromatin components (DNA and histones) and chromatin regulators. I am particularly focused on the study of the key plant-specific trithorax factor ULTRAPETALA1 (ULT1), which enables the transition of target genes from a repressed to an active state (and vice versa), thus inducing essential developmental transitions such as flowering and cell differentiation during floral organogenesis. Using an integrated genetics and biochemistry approach, I show that ULT1 has a multi-dimensional effect on chromatin regulation. In the first chapter of my PhD, I assess ULT1 global and genome-wide effect on epigenetic marks. I report that ULT1 acts as a PRC2 cofactor capable of directly enhancing the catalytic activity of PRC2 on chromatin. I also show that ULT1 plays a role in the dynamics of DNA methylation in Arabidopsis. Finally, I describe a straightforward method for purifying histones for proteomic analysis by mass spectrometry, which I aimed to use in order to answer the effect of ULT1 on histone marks. In the second chapter, I address how ULT1 reaches its targets at the chromatin. I show that ULT1 acts through affinities with post-translational modifications of histones, DNA and RNA. Through its positively charged surface, ULT1 can interact with DNA without apparent DNA motif specificity. ULT1 can also interact with a long non-coding RNA produced from one of its target genes in a PRC2-dependent manner, to control floral meristem termination. Finally, I show that ULT1 regulates flowering time through an H3K36me3-dependent mechanism, potentially by interacting directly with histone marks. Altogether, the results acquired in the course of my PhD indicate that ULT1 may constitute a scaffold protein capable of switching the chromatin state and transcriptional status of corresponding loci from off to on, and vice versa. These results thus reveal a novel chromatin regulatory function and uncover new avenues for understanding trxG/PcG interplay in eukaryotes.​​​​​
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