From the above discussion it can be appreciated that the major unknowns to advancing our understanding of nucleosome and chromatin structure and functions are: 1) the binding sites of the histone N- and C-terminal domains in native nucleosomes and in chromatin; 2) the effects of histone reversible chemical modifications of phosphorylations, acetylations and ubiquitinations on the binding of the histone N- and C-terminal domains in nucleosome and chromatin structures; 3) the path(s) of the linker DNA between nucleosome in the different orders of chromatin structure; 4) the position of the globular, N- and C-terminal domains of linker histones in the nucleosome and chromatin structures; and 5) the lack of a detailed structure for the 30 nm chromatin fiber. The above unknowns provide formidable challenges for future researchers.