Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci

Abstract

Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters during their early activation in vivo, using high-resolution circular chromosome conformation capture. Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. These local 3D dynamics occur within a framework of constitutive interactions within the surrounding Topological Associated Domains, indicating that this regulation process is mostly cluster intrinsic. The step-wise progression in time is fixed at various body levels and thus can account for the chromatin architectures previously described at a later stage for different anterior to posterior levels.DOI: http://dx.doi.org/10.7554/eLife.02557.001

Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders

“…1B). Similar results have been found in mammals and Drosophila, indicating that some genes have a preassembled 3D chromatin architecture that likely facilitates precise gene regulation (6,13,14,16,17). The overall 3D interaction map remains constant throughout development, with some local contact variations, likely linked to particular cis-regulatory element activation (Fig.…”

Nanoscale spatial organization of the HoxD gene cluster in distinct transcriptional states

“…35, the latter being even weaker when ES cells were cultured in 2i medium (36)]. It was also noticed that Hoxd genes established many more interactions with the neighboring gene deserts in ES cells than in brain cells (35), where most interactions involved the gene cluster itself, further suggesting a more decompacted configuration of the locus in ES cells. Therefore, the vast majority of ES cells may display decompacted chromatin at their Hox loci.…”

“…A significant elongation of the gene cluster was also scored in ES cells, even though the entire HoxD cluster is labeled with both H3K4me3 and H3K27me3 chromatin marks (22,28,30) associated with the formation of local chromatin domains (23,35), in contrast with the idea that Hox clusters adopt a "closed" conformation whenever genes are silent (23). In ES cells, however, the 4C interaction patterns are much weaker than in brain cells (35), probably because of the presence of bivalent chromatin marks and the concomitant reduced amount of H3K27me3 modifications [ Fig.…”

“…In ES cells, however, the 4C interaction patterns are much weaker than in brain cells (35), probably because of the presence of bivalent chromatin marks and the concomitant reduced amount of H3K27me3 modifications [ Fig. 1 and figure S1 in ref.…”

Control of Hoxd gene transcription in the mammary bud by hijacking a preexisting regulatory landscape

“…The particular topology of chromatin domains at Hox loci could have triggered the emergence of novel enhancers, through preexisting structural and regulatory contacts (16). Noteworthy, region CS38-CS40 is located at the boundary between the two sub-TADs of the T-DOM and was reported to establish robust contacts with the HoxD cluster in all tissues analyzed thus far, regardless of the transcriptional state of the gene cluster (17,53,64). These constitutive contacts may be associated with the presence of several CTCF binding sites clustered in this region.…”