Heterocromatin

Heterochromatin is a compact form of chromatin found in eukaryotic genomes that is transcriptionally inactive or highly repressed. It is distinguished from euchromatin by its dense organization, reduced accessibility to transcription factors, and specific biochemical markers. The term derives from the Greek words “hetero” (different) and “chromatin” (colored), reflecting its distinct staining properties in microscopic preparations.

Two principal classes of heterochromatin exist. Constitutive heterochromatin is present in nearly all cells and consists largely of repetitive DNA such as satellite sequences, transposable elements, and centromeric repeats. It is usually permanently silenced and is essential for maintaining chromosome structure and stability, particularly at centromeres and telomeres. Facultative heterochromatin, in contrast, can be reversible and is involved in the regulation of specific genes. Examples include polycomb-repressed domains that silence developmental genes during differentiation.

Heterochromatin is associated with characteristic histone modifications, most notably histone H3 lysine 9 trimethylation (H3K9me3) and histone H4 lysine 20 methylation (H4K20me3). These marks recruit proteins such as heterochromatin protein 1 (HP1) and chromodomain helicase DNA binding protein 1 (CHD1) that help compact the DNA and create a repressive environment. DNA methylation, particularly at CpG dinucleotides, is also common in heterochromatic regions and contributes to the maintenance of transcriptional silencing.

The formation and maintenance of heterochromatin involve a complex interplay of epigenetic marks, chromatin remodelers, and noncoding RNAs. Changes in heterochromatin structure have been implicated in aging, disease, and cellular differentiation. Techniques such as fluorescence in situ hybridization, chromatin immunoprecipitation followed by sequencing (ChIP‑seq), and microscopic staining with dyes like DAPI reveal heterochromatic regions as intensely stained, highly condensed domains.