The basal unit of information storage in the cell is at the level of the DNA sequence. Additional regulatory strata are possible because of the packaging of DNA in a highly compacted chromatin structure. Furthermore, DNA nucleotides can carry chemical modifications that change the interaction with histones, the scaffold proteins of chromatin, and therefore, the level of compaction or DNA accessibility.
Histones are small, highly basic proteins. Two pairs of H3, H4, H2A and H2B constitute together an octamer, around which about 147 bp of DNA are wrapped to build up the basic unit of chromatin: the nucleosome. Histones carry diverse covalent post-translational modifications (PTMs) such as acetylation, phosphorylation, methylation, ubiquitination and ADP-ribosylation. These dynamic and often evolutionary conserved modifications act in combination to establish distinct chromatin states. Histone PTMs can be read and interpreted by specific proteins, which subsequently influence numerous biological processes including transcription, replication, chromosome maintenance and cell division.
The addition of a methyl group to cytosine bases of the DNA to form 5- methylcytosine, referred to as DNA methylation, is another layer of epigenetic control that can stabilize repressed chromatin domains. DNA methylation occurs in both prokaryotes and eukaryotes. Although absent in budding and fission yeast as well as in Caenorhabditis elegans, this mark is prominent in fungi, plants and vertebrates (He et al., 2011). In plants, DNA methylation occurs in the contexts of CG, CHG and CHH (H = A, C, or T) and is highly abundant in pericentromeric regions as well as other repetitive elements. DNA methylation in the CG sequence context also occurs in the transcribed region of nearly one third of expressed genes in Arabidopsis thaliana. Several studies have revealed the complex relationship between DNA methylation and histone PTMs. This evidence points towards the existence of multiple feedback loops controlling the dynamics of deposition of DNA methylation and histone modifiers.
The spatiotemporal combination of histone modifications and DNA methylation determines the state of the chromatin, playing a major role in the modulation of gene expression and cell-fate decisions. The aim of my PhD is to expand the epigenetic code in Arabidopsis and to integrate this knowledge into the regulatory networks that drive cell-fate decisions, progression and maintenance. Using multiple genome-wide technologies and computational tools, I intend to characterize the chromatin states and underlying modifications triggered by/in control of development and stress signal responses.