In living cells, structural proteins such as the linker histone H1 and the high mobility group (HMG) proteins continuously modulate the local and global architecture of the chromatin fiber and affect the binding of regulatory factors to their nucleosomal targets.
ISWI complexes are recruited to their nucleosomal substrates through their interactions with DNA-binding domains with the extranucleosomal DNA and/or by recognizing histone modifications to modulate chromatin structure [ 43, 44].
HMGN proteins specifically bind to the nucleosome core particle through a highly conserved "nucleosomal binding domain" (NBD) and reduce chromatin compaction.
Although nucleosome-depleted regions are necessary for most TFBSs, some TFs may bind to nucleosomal DNA without nucleosome reorganization.
Pioneer factors, such as FoxA, GATA, and PU.1, can bind to nucleosomal DNA and displace nucleosomes to help other TFs access their sites [ 33].
In addition, in contrast to yeast, repressors, rather than activators, were more likely to bind to nucleosomal DNA in the human cells, and nucleosomes around repressor sites were better positioned in vivo.
Previous studies have suggested that TF NF-κB p50 can bind to nucleosomal DNA without perturbing the overall structure of the nucleosome [ 34].
Finally, the ability of Chd1-DBD to bind to nucleosomal DNA was investigated.
Repressors were more likely to bind to nucleosomal DNA, which might require catalyzed remodeling, in the human genome.
