Genomic landscape studies have revealed that frequently mutated pathways in ACC often involve in chromatin remodeling, which interfere multiple histone related proteins.
The presence of multiple histone binding proteins in the NURD complex may account for high affinity interaction between NURD and H3 tail and broad function of NURD in chromatin remodeling, transcription, DNA damage repair and cell cycle.
PcG proteins repress transcription compacting the chromatin through DNA methylation and multiple histone modifications following a multistep protein recruitment that prevents mRNA elongation [ 49, 50].
Different histone PTMs deposited across multiple residues on histone proteins generate a combinatorial pattern.
To add to this complexity, the chromatin structure is also influenced by effector or "reader" proteins that recognize single or multiple histone PTMs (Fig. 1B).
The two epigenetic alterations we know the most about are methylation, a change on the DNA strand, and histone modification, a chemical reaction that regulates how tightly or loosely DNA wraps around a histone protein.
The histone protein of Hfx.
The diversity of arginine methylation sites on histone proteins provides multiple routes to directly link arginine methylation to the epigenetic regulation of gene expression.
Moreover, the N-termini of histone proteins contain multiple lysine residues and are accessible to covalent modifications such as acetylation, methylation, sumoylation, biotinylation, phosphorylation, glycosylation, and ADP-ribosylation, thus allowing regulation of gene transcription (Fig. 1) [ 4, 5, 33– 33].
Bromodomain-containing protein 9 (BRD9), an epigenetic "reader" of acetylated lysines on post-translationally modified histone proteins, is upregulated in multiple cancer cell lines.
