Eukaryotes tune the transcriptional activity of their genome by altering the 
nucleosome core particle through multiple chemical processes. In particular, 
replacement of the canonical H2A histone with the variants macroH2A and H2A.Z 
has been shown to affect DNA accessibility and nucleosome stability; however, 
the processes by which this occurs remain poorly understood. In this study, we 
elucidate the molecular mechanisms of these variants with an extensive molecular 
dynamics study of the canonical nucleosome along with three variant-containing 
structures: H2A.Z, macroH2A, and an H2A mutant with macroH2A-like L1 loops. 
Simulation results show that variant L1 loops play a pivotal role in stabilizing 
DNA binding to the octamer through direct interactions, core structural 
rearrangements, and altered allosteric networks in the nucleosome. All variants 
influence dynamics; however, macroH2A-like systems have the largest effect on 
energetics. In addition, we provide a comprehensive analysis of allosteric 
networks in the nucleosome and demonstrate that variants take advantage of 
stronger interactions between L1 loops to propagate dynamics throughout the 
complex. Furthermore, we show that posttranslational modifications are enriched 
at key locations in these networks. Taken together, these results provide, to 
our knowledge, new insights into the relationship between the structure, 
dynamics, and function of the nucleosome core particle and chromatin fibers, and 
how they are influenced by chromatin remodeling factors.