Project description:Chromosomes are three-dimensional structures in the nucleus that are organized at multiple levels. Studies in mammals have shown that chromosomes segregate in active and inactive compartments (A and B, resp.). A compartments have high transcription activity, high GC-content and replicate early in S-phase. B compartments on the other hand are transcriptionally inactive, have low CG content are often found at the nuclear periphery. Every compartment is further divided into megabase-sized Topologically Associated Domains (TADs), the functional units of gene regulation. Regions within such a domain preferentially interact with each other. TAD positions are conserved between mouse and human genomes. However, it is unclear if non-mammalian vertebrates also show these organizational features and how these change throughout development. We have generated Hi-C maps for zebrafish embryos and show that the structural features of mammalian genomes (A/B-compartments and TADs) are also found in this species. We find that the genes within TADs show spatial co-expression. Moreover, the order of genes within a TAD is conserved to other vertebrate species. One of the key features of development is the switch from maternally loaded mRNAs to the transcriptional activation of the zygotic genome, known as Zygotic Genome Activation (ZGA). Prior to ZGA we see both TADs and compartments. Paradoxically, after the initiation of transcription, TADs and compartments completely disappear. These features are progressively re-established in the following developmental stages. Our results show that chromosome conformation can be formed independent of transcription. Analysis of active enhancer and promoter marks after ZGA showed that promoters and enhancers are enriched at future TAD-boundaries. Later in time, when TADs are present, the enrichment of active enhancers at the TAD-boundaries is lost. These data suggest that proximal enhancer-promoter interactions are needed for gene regulation when TADs are not in place. The loss of both TADs and compartments represent an interesting avenue for the further study of factors involved in the formation of the structural features of vertebrate chromosomes.

Dataset Information

Systemic Loss and Gain of Chromatin Architecture throughout Zebrafish Development.

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