Heterochromatin Domains: Uncoupling Epigenetic Modifications and Chromatin Structural Parameters

The mammalian genome is organized into silenced and active domains, which are constituted by chromatin fibres. The fibres are comprised of nucleosome subunits in which nearly two turns of DNA wrap around a histone protein core. This first order of DNA structure is known as the 10 nm chromatin fibre. Almost since the discovery of the nucleosome our widely accepted paradigm of genome regulation has included higher orders of chromatin organization based on the coiling or folding of the 10 nm chromatin fibre into the 30 nm chromatin fibre. These 30 nm chromatin fibres could occlude activating factors, thereby preventing transcription of genomic domains. Thus, the transition between the euchromatin “open” 10 nm and the heterochromatin “closed” 30 nm chromatin fibre would ultimately dictate genome activation and silencing. Additionally, these 30 nm fibres were thought to be further condensed into large structural heterochromatin domains defined biochemically by specific post-translational modifications of their nucleosomes’ core histones.