Research Fellows Directory
Dr Varodom Charoensawan
Wellcome Trust Sanger Institute
Transcription factors (TFs) and histone octamers are the two most abundant DNA-binding proteins in eukaryotic nuclei, and their dynamic interplay coordinates transcriptional programmes in cells. Despite their importance, it is not clear how TFs and nucleosomes are positioned under different cellular conditions to orchestrate transcription. Our previous computational model in yeast showed two major "interaction modes" of TFs and nucleosomal histones: histone-correlated TFs that tend to function as activators; and histone-anti-correlated TFs, which are mostly repressors (Charoensawan et al. Mol Cell, 2012). To investigate whether such "general rules" also apply to other biological systems, we are currently following up this prediction using competition ChIP-seq of histone-depleted yeast, as well as in multicellular eukaryotes including plant and T helper cell models.
In collaboration with the Teichmann group at the Sanger Institute-EBI Single-Cell Genomics Centre, Wellcome Trust Genome Campus, we propose to combine the high-resolution genomics view obtained by single-cell RNA-sequencing with open chromatin patterns at the single cell level (ATAC-seq, ChIP-seq), to characterise the turnover of TF-nucleosome DNA-binding configurations in differentiating mouse CD4+ T cells. By integrating these new data with known binding sites of eukaryotic TFs, we will infer the dynamics of TF-nucleosome interplay in CD4+ T cell differentiation, quantify the proportions of individual cells that take up different TF-nucleosome interaction modes, dissect technical noise and biological variation, and reveal how these contribute to overall expression level dynamics.
Interests and expertise (Subject groups)