Somatic epimutations cap genetic determinism in the human diploid chromatin epigenome.

Somatic chromatin epimutations in human cells create mitotically stable, non-genetically deterministic alterations, with the HLA locus showing the highest haplotype-selective accessibility.

• Why it matters: Understanding how chromatin regulation varies between genomes in diploid human cells is crucial for insights into development and disease, especially as these epimutations may influence gene expression independently of DNA sequence.
• What they did: Fiber-seq inferred regulatory elements (FIRE) were used to generate a comprehensive, quantitative map of accessible chromatin across the 6 Gbp human genome, revealing haplotype-selective chromatin accessibility and somatic epimutations.
• The result: The study shows that somatic epimutations are propagated through clonal expansion, creating stable chromatin changes that are not dictated by genetic variation, and highlights the HLA locus as having the most haplotype-specific accessibility in immune cells.