Genomic DNA in the eukaryotic nucleus is hierarchically packaged by histones into chromatin to fit inside the nucleus. The dynamics of higher-order chromatin compaction play a critical role in transcription and other biological processes inherent to DNA. Many factors, including histone variants, histone modifications, DNA methylation and the binding of non-histone architectural proteins regulate the structure of chromatin. Although the structure of nucleosomes, the fundamental repeating unit of chromatin, is clear, there is still much discussion on the higher-order levels of chromatin structure, including the detailed structural information for the “30-nm” chromatin fibers. A review published in CURRENT OPINION IN GENETICS & DEVELOPMENT (2011, 21: 175-186) by Dr Guohong Li focuses on the recent progress in elucidating the structure of the 30-nm chromatin fiber. The structural plasticity/dynamics and epigenetic inheritance of higher-order chromatin and the roles of chromatin higher-order organization in eukaryotic gene regulation have also been discussed in the review.

Hierarchical folding and Plasticity of higher-order chromatin structures: A general scheme represent the folding of chromatin from 11-nm nucleosomal arrays (beads-on-string) to higher order chromatin structures including 30-nm chromatin fiber, fiber-fiber association, chromatin looping and positioning. Factors proposed to affect changes between different chromatin structures are shown.(by Dr Guohong Li ect.)

Dr Guohong Li’s group in the Institute of Biophysics, Chinese Academy of Sciences has established awell-defined in vitro system to investigate the chromatin higher-order structures and their related epigenetic regulation functions. The chromatin fibers can be reconstituted on tandem repeats of “widom 601 nucleosome positioning” sequence by the salt dialysis technique. In addition, more native chromatin fiber can be reconstituted on native DNA sequence by ATP-dependent chromatin assembly method. Furthermore, several techniques have been developed in the group to investigate the structural dynamics of the reconstituted chromatin fibers in vitro, including the analytical ultracentrifuge (AUC), EM/cryo-EM and FRET methods. In the meanwhile, an in-vitro transcription system has been developed to investigate the impact of chromatin dynamics on gene transcription. Using these systems, the molecular mechanisms of epigenetic regulation of histone modifications and histone variants on gene transcription can be further clarified by correlating the dynamics of chromatin structures with their gene functions.