histonkoden

Histonkoden, or the histone code, refers to the proposed set of covalent post-translational modifications on histone proteins that regulate chromatin structure and gene expression. In eukaryotic cells, histones H2A, H2B, H3, and H4 carry modifications on their tail regions, including methylation, acetylation, phosphorylation, ubiquitination, and sumoylation. The histone code hypothesis suggests that specific combinations of these marks create binding sites for reader proteins that recruit chromatin modifiers and transcriptional machinery, thereby influencing transcriptional outcomes. Enzymes act as writers to add marks, erasers to remove them, and readers to interpret them.

Common marks include H3K4me3 at active promoters; H3K27ac at active enhancers; H3K36me3 along transcribed gene bodies; and H3K9me3 or H3K27me3 associated with heterochromatin and Polycomb-mediated repression. The meaning of a given mark often depends on neighboring marks and genomic context, reflecting a combinatorial rather than a simple one-to-one code. Interactions with DNA methylation and chromatin remodelers further shape chromatin states.

The histone code framework has driven extensive genome-wide mapping and proteomic studies and is central to understanding development, differentiation, and disease, including cancer where histone-modifying enzymes are frequently dysregulated. Critics note that the model may be an oversimplification and emphasize a network of context-dependent interactions among multiple modifications.

Research approaches include chromatin immunoprecipitation followed by sequencing (ChIP-seq), mass spectrometry of histone tails, and newer methods like CUT&RUN. The concept remains a foundational idea in epigenetics.