histonemodifying

Histone modification refers to covalent post-translational modifications of histone proteins, which package and organize DNA into chromatin. These chemical marks commonly occur on histone tails and, less frequently, on the core histone domains. They influence chromatin structure and accessibility, thereby regulating transcription, DNA repair, replication, and other DNA-templated processes.

The major types of histone modifications include acetylation, methylation, phosphorylation, ubiquitination, and, less commonly, sumoylation or ADP-ribosylation. Lysine and sometimes arginine residues on histone tails are frequent sites for acetylation and methylation. Acetylation generally correlates with open chromatin and active transcription, while methylation can be associated with either activation or repression depending on the residue and degree of methylation. Phosphorylation often relates to chromosome condensation during mitosis or DNA damage responses, and ubiquitination of histones can influence nucleosome stability and transcriptional outcomes.

Histone-modifying enzymes are categorized as writers, erasers, and readers. Writers add chemical groups (for example, histone acetyltransferases, methyltransferases), erasers remove them (deacetylases, demethylases), and readers recognize specific modifications to recruit other proteins that affect chromatin states. Examples include acetyltransferases such as p300/CBP, methyltransferases that install methyl marks on H3K4 or H3K27, and bromodomain or chromodomain-containing proteins that read acetylated or methylated lysines, respectively.

Biological significance of histone modifications spans development, differentiation, aging, and disease. Disturbances in histone-modifying activities are linked to cancers, neurological disorders, and metabolic diseases. Research employs techniques like chromatin immunoprecipitation sequencing and mass spectrometry to map and quantify histone marks. The combined pattern of histone modifications contributes to the histone code, a framework describing context-dependent regulation of gene expression through combinatorial marks.