Proteomics of the Mouse Epigenome: Qualitative & Quantitative Analysis of Post-translational Modifications of Chromatin in the Brain and Germline

We are studying post-translational modifications (PTMs) on chromatin in the mouse brain and sperm and their involvement in the epigenetic regulation of gene expression. We are specifically investigating the role of histone PTMs in cognitive functions and the role of histone and protamine PTMs in the transgenerational transmission of epigenetic marks. Histones are proteins that package and order the DNA into nucleosomes in the chromatin of eukaryotic cells. In sperm cells, histones are largely replaced by protamines (smaller proteins) to form tightly packed chromatin. The combination of histone PTMs such as phosphorylation, acetylation and methylation form a histone code, which regulates gene transcription by altering chromatin conformation and accessibility to the transcriptional machinery. Building on our previous work on epigenetics in learning and memory, we are investigating the role of specific histone PTMs in the mouse brain and male germline, and are identifying and quantifying histones, protamines and their PTMs using high accuracy tandem mass spectrometry technologies. Our work recently revealed novel PTMs on histones and protamines.

Keywords: Epigenetics, Neuroproteomics, Mass Spectrometry, PTM, Bottom-up, Top-down