Chromatinmodifying

Chromatin modification, also described as chromatin-modifying activity, comprises biochemical processes that alter chromatin structure and function without changing the DNA sequence. These processes include covalent histone modifications, DNA methylation, and ATP-dependent remodeling of nucleosomes, which collectively regulate genome accessibility and transcription.

Covalent histone modifications include acetylation, methylation, phosphorylation, ubiquitination, and sumoylation. Enzymes that add marks are known as writers, those that remove marks as erasers, and proteins that recognize marks as readers. DNA methylation, mainly at CpG sites, is catalyzed by DNA methyltransferases and can be reversed by ten-eleven translocation enzymes. Chromatin remodeling complexes use energy from ATP hydrolysis to reposition, eject, or replace nucleosomes.

These modifications form an epigenetic layer that controls processes such as development, differentiation, DNA replication, and repair. The effect of a modification depends on its type and genomic context (for example, H3K4me3 is associated with active promoters, while H3K27me3 is repressive). Crosstalk between marks underpins the so-called histone code.

Dysregulation of chromatin-modifying activities is linked to diseases, including cancer and neurodevelopmental disorders. Research methods include chromatin immunoprecipitation sequencing (ChIP-seq), ATAC-seq, CUT&RUN, and bisulfite sequencing. Therapeutic approaches target chromatin modifiers with inhibitors of HDACs or DNMTs, illustrating the clinical relevance of chromatin modification.