Regulation of gene expression by acetylation and lactylation of histone proteins

In eukaryotic cells, DNA wraps around histone proteins to form chromatin. Dynamic modification of histones by various chemical structures allows for fine regulation of gene expression. Alterations in these complex regulatory mechanisms are responsible for many diseases. Acetylation of histone lysines is known to induce gene expression. Other structures can be added to histones, whose effects on transcription remain largely unclear. Most of them, such as lactylation discovered in 2019, depend on cellular metabolism. We are studying this new modification in murine spermatogenesis: this process of cell differentiation is an ideal model for studying transcription regulation, due to dramatic changes in chromatin composition and gene expression patterns. We have established the distribution of acetylated and lactylated marks on three lysines of histone H3 across the genome. The aim of this thesis is to contribute to deciphering the “histone language,” first by studying the role of lactylations on the transcriptional program. Next, the prediction of chromatin states will be refined by integrating our new data with numerous available epigenomic data within neural network models.