Chromosome Structural Mechanics Dictates the Local Spreading of Epigenetic Marks

We present a theoretical model that demonstrates the integral role chromosome organization and structural mechanics play in the spreading of histone modifications involved in epigenetic regulation. Our model shows that heterogeneous nucleosome positioning, and the resulting position-dependent mechanical properties, must be included to reproduce several qualitative features of experimental data of histone methylation spreading around an artificially induced "nucleation site." We show that our model recreates both the extent of spreading and the presence of a subdominant peak upstream of the transcription start site. Our model indicates that the spreading of epigenetic modifications is sensitive to heterogeneity in chromatin organization and the resulting variability in the chromatin's mechanical properties, suggesting that nucleosome spacing can directly control the conferral of epigenetic marks by modifying the structural mechanics of the chromosome. It further illustrates how the physical organization of the DNA polymer may play a significant role in re-establishing the epigenetic code upon cell division.