Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain

Abstract

Embryogenesis requires the precise activation and repression of many transcriptional regulators. The Polycomb group proteins and the associated H3K27me3 histone mark are essential to maintain the inactive state of many of these genes. Mammalian Hox genes are targets of Polycomb proteins and form local 3D clusters centered on the H3K27me3 mark. More distal contacts have also been described, yet their selectivity, dynamics, and relation to other layers of chromatin organization remained elusive. We report that repressed Hox genes form mutual intra-and interchromosomal interactions with other genes located in strong domains labeled by H3K27me3. These interactions occur in a central and active nuclear environment that consists of the HiC compartment A, away from peripheral lamina-associated domains. Interactions are independent of nearby H3K27me3-marked loci and determined by chromosomal distance and cell-type-specific scaling factors, thus inducing a moderate reorganization during embryogenesis. These results provide a simplified view of nuclear organization whereby Polycomb proteins may have evolved to repress genes located in gene-dense regions whose position is restricted to central, active, nuclear environments.Hox genes | Polycomb | long-range chromatin contacts | nuclear organization

Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding

“…In summary, these findings suggest that chromatin domains interact dynamically and preferentially in a homotypic fashion: Active promoters contact more often active chromatin sites than expected by the genome-wide distribution of chromatin states, and vice versa, repressed promoters contact repressed chromatin sites more often, in line with the findings reported for the HoxD cluster (Noordermeer et al 2011Vieux-Rochas et al 2015).…”

Comprehensive characterization of neutrophil genome topology

“…3E,F). Previous studies have revealed that, in embryonic stem cells, genomic regions associated with the HoxD locus interact with other regions that are characterized by a high abundance of H3K27me3 to generate a network of intrachromosomal and interchromosomal interactions across the A compartment (Denholtz et al 2013;Vieux-Rochas et al 2015). In contrast, we found that, in neutrophils, a network of genomic interactions marked by H3K27me3 was associated with the B compartment.…”

The second decade of 3C technologies: detailed insights into nuclear organization

“…An essentially similar approach employing a four-cutter to digest cross-linked chromatin but using probes directed to DNase I-hypersensitive sites confirmed the clustering of H3K27me3/polycomb-marked regions like the Hox gene clusters in ESCs (Denholtz et al 2013;Vieux-Rochas et al 2015). mESCs are known to exist in different states, with serum ESCs being more similar to post-implantation pluripotent stem cells and more developmentally primed than ground-state pluripotent 2i cultured ESCs.…”

“…Spatial clustering of TADs with a similar chromatin signature has also been observed in other studies. Polycomb group protein-bound regions such as the Hox genes spatially cluster in the nuclear space of ESCs (Denholtz et al 2013;Vieux-Rochas et al 2015), possibly even forming a spatial network with other developmental genes that are silenced but poised to be activated upon differentiation . Furthermore, TADs that are rich in binding sites for key pluripotency factors cluster in ESC nuclei Zhang et al 2013), as do regions in somatic cells that efficiently recruit their corresponding cellular identity factors (Lin et al 2012;Krijger et al 2016).…”