Small chromosomal regions position themselves autonomously according to their chromatin class

Abstract

The spatial arrangement of chromatin is linked to the regulation of nuclear processes. One striking aspect of nuclear organization is the spatial segregation of heterochromatic and euchromatic domains. The mechanisms of this chromatin segregation are still poorly understood. In this work, we investigated the link between the primary genomic sequence and chromatin domains. We analyzed the spatial intranuclear arrangement of a human artificial chromosome (HAC) in a xenospecific mouse background in comparison to an orthologous region of native mouse chromosome. The two orthologous regions include segments that can be assigned to three major chromatin classes according to their gene abundance and repeat repertoire: (1) gene-rich and SINE-rich euchromatin; (2) gene-poor and LINE/LTR-rich heterochromatin; and (3) gene-depleted and satellite DNA-containing constitutive heterochromatin. We show, using fluorescence in situ hybridization (FISH) and 4C-seq technologies, that chromatin segments ranging from 0.6 to 3 Mb cluster with segments of the same chromatin class. As a consequence, the chromatin segments acquire corresponding positions in the nucleus irrespective of their chromosomal context, thereby strongly suggesting that this is their autonomous property. Interactions with the nuclear lamina, although largely retained in the HAC, reveal less autonomy. Taken together, our results suggest that building of a functional nucleus is largely a self-organizing process based on mutual recognition of chromosome segments belonging to the major chromatin classes.

Compartment-dependent chromatin interaction dynamics revealed by liquid chromatin Hi-C

“…This is in agreement with recent independent locus-specific experiments. First, previous studies had suggested that regions of several hundred kb were long enough to correctly position themselves in vivo according to their chromatin state in the corresponding compartment (van de Werken et al, 2017). Second, super-enhancers that typically range in size between 10 and 25 kb were found to associate both in cis and in trans, especially in the absence of cohesin (Rao et al, 2017), indicating that interactions between these 10-25 kb elements are stable enough to facilitate their clustering.…”

TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation

“…Cohesins, together with DNA/chromatin elements (2). In this context, the expansion of several families of transposable elements (TE) has provided new regulatory network for coordinated control of gene expression (3) and enabled more sophisticated avenues for genome organization (4,5). Short Interspersed Elements (SINEs), in particular Alu elements (AEs), represent the largest fraction of TE which have also evolved proto-enhancers function in the human genome (6).…”

“…Since AEs have been shown to evolve towards proto-enhancer function and the epigenetic state of enhancers participates in forging genome topology and gene expression (5,6), TFIIIC might help in reorganizing the landscape of chromatin loops upon SS. To explore this possibility, we compared genomic contacts by in nucleo Hi-C (24) and transcript levels by mRNA-seq in T47D cells grown in the presence of absence of serum.…”

Heterochromatin drives organization of conventional and inverted nuclei

“…Our model is agnostic of whether such attraction between heterochromatin is caused by affinity between homotypic repetitive elements 30,31 , or mediated by other proteins (e.g. HP1) 32,33 .…”