Multi-Scale Spatio-Temporal Dynamics of Histone Modifications

Abstract

Epigenetic mechanisms can regulate gene expression patterns in response to environmental alterations. Histone modifications are essential components of transgenerational epigenetics, yet little is known about their spatial distribution at short and long time scales. We investigated the genome-wide dynamics of five histone modifications (H3K27me3, H4K20me1, H3K36me1, H3K4me3, and H3K9me3), on C. elegans by growing P0 in bacterial agar plates, F1 in liquid, and F2 back in agar. Two different liquid cultures were used to explore how diet affects epigenetics: a bacterial food source, and a chemically-defined axenic broth. For the F1 generations, about half of the gene promoters are occupied by multiple histone modifications, as compared to single histone modifications predominantly observed in P0 animals. This result indicates that multiple histone marks can regulate single genes, or that different cell types are regulated by different marks. We find that H4K20me1 and H3K36me1 distributions are retained by F2 from a bacterial liquid culture, whereas these histone marks are rearranged by F2 from axenic liquid cultures, implying a role of these marks in dietary-related metabolism. Additionally, histone modifications H3K27me3 and H3K4me3 display highly constant distributions, while the others exhibited up to eight-fold difference in the number of genes (promoters) they associate with from P0 to F2. These results suggest that the epigenetic memory levels of histone marks affect the distribution dynamics of histone modifications on the genome. Our bioinformatics results demonstrated correlation at the single-cell level with fluorescence microscopy for the dynamics of histone modifications in embryos. For example, we show that at earlier stages of embryogenesis, H4K20me1 is distributed to a subset of cells and it becomes broadly distributed at the later (>64 cell) stages. Our correlative approach, employing bioinformatics and fluorescence microscopy, enables the observation of short- and long-term dynamics of histone modifications.