Fig. 4

Model for nucleosome instability over the body of broad epigenetic domain genes. A Nucleosomes are being removed and reassembled due to the action of CHD1. Core histone [CH] PTMs would be removed with the displaced nucleosome (lower part of A) or by chromatin modifying enzymes (upper part of A). Jumonji domain containing 6 (JMJD6) is thought to demethylate H4R3me2a [136]. Nucleosome reassembly would allow for incorporation of histone variants such as H3.3 and a new set of core histone PTMs. Methods such as FAIRE-seq and DNase-seq will identify the nucleosome free regions. Regions lacking nucleosomes are detected by FAIRE-seq, and modified nucleosomes by ChIP-seq (color coded as in Fig. 3 to represent active marks present on all nucleosomes). The histone marks typically overlap over multi-modified nucleosomes but demonstrated individually for simplicity. B Doxorubicin intercalates into DNA of broad epigenetic domain displacing core histones. H3K4me3-modified nucleosomes are selectively dissociated when doxorubicin intercalates into these regions. This results in the formation of nucleosome-free regions (NFR) following the displacement of H3K4me3-modified nucleosomes