Chromatin-Driven Behavior of Topologically Associating Domains

Abstract

Metazoan genomes are highly organized inside the cell nucleus. Topologically associating domains (TADs) represent the building blocks of genome organization, but their linear modularity does not explain alone their spatial organization. Indeed, the chromatin type adorning a TAD can shape its structure and drives its nuclear positioning and its function. Genome-wide association studies revealed mainly four chromatin types: active chromatin, Polycomb-repressed chromatin, null chromatin and constitutive heterochromatin. In this review, we will describe the main three-dimensional features of each chromatin type and finally their relationships with TAD organization and epigenetic memory.

Nuclear compartmentalization of DNA repair

“…Heterochromatin can be distinguished in three main forms based on histone modifications and protein composition: constitutive, facultative and null chromatin [37]. Constitutive it is the most highly compacted form of heterochromatin and it is enriched in deacetylated histones and histone H3 trimethylation on lysine 9 (H3K9me3), as well as non-histone repressive proteins like KAP1 and the heterochromatin protein 1 (HP1) that bind H3K9me3 [38][39][40].…”

“…Constitutive it is the most highly compacted form of heterochromatin and it is enriched in deacetylated histones and histone H3 trimethylation on lysine 9 (H3K9me3), as well as non-histone repressive proteins like KAP1 and the heterochromatin protein 1 (HP1) that bind H3K9me3 [38][39][40]. Facultative heterochromatin is more plastic and its state of compaction can change during differentiation or after stimuli [37]. It is characterized by histone H3 trimethylation on lysine 27 (H3K27me3) and binding of the Polycomb repressive complexes [37].…”

“…Facultative heterochromatin is more plastic and its state of compaction can change during differentiation or after stimuli [37]. It is characterized by histone H3 trimethylation on lysine 27 (H3K27me3) and binding of the Polycomb repressive complexes [37]. Null chromatin although covers a large portion of the genome, it is not specifically enriched in any of the histone modifications that characterize the other two heterochromatin forms.…”

Coming to terms with chromatin structure

“…We therefore believe that these globular domains, their exact size yet to be determined, should be considered as higher order chromatin structures. These structures and their boundaries may be crucial for a higher order level of functional chromatin organization (as discussed and reviewed in Ciabrelli and Cavalli 2015;Nora et al 2013;Sanyal et al 2011).…”

“…The exact number of chromatin types described in the separate studies varies due to the algorithm used and other parameters. However, at least four main types can be described: one active and three repressive types (Ciabrelli and Cavalli 2015). Further, whereas heterochromatin was thought to be transcriptionally inert and euchromatin transcriptionally active, we now know that this distinction is not absolute-some transcription can occur in the heterochromatin (reviewed in Enukashvily and Ponomartsev 2013;Hall et al 2012;Saksouk et al 2015).…”