Systemic Loss and Gain of Chromatin Architecture throughout Zebrafish Development

Lucas J.T Kaaij,Robin H Van Der Weide,René F Ketting,Elzo De Wit

doi:10.1016/j.celrep.2018.06.003

Abstract

SummaryThe spatial organization of chromosomes is critical in establishing gene expression programs. We generated in situ Hi-C maps throughout zebrafish development to gain insight into higher-order chromatin organization and dynamics. Zebrafish chromosomes segregate in active and inactive chromatin (A/B compartments), which are further organized into topologically associating domains (TADs). Zebrafish A/B compartments and TADs have genomic features similar to those of their mammalian counterparts, including evolutionary conservation and enrichment of CTCF binding sites at TAD borders. At the earliest time point, when there is no zygotic transcription, the genome is highly structured. After zygotic genome activation (ZGA), the genome loses structural features, which are re-established throughout early development. Despite the absence of structural features, we see clustering of super-enhancers in the 3D genome. Our results provide insight into vertebrate genome organization and demonstrate that the developing zebrafish embryo is a powerful model system to study the dynamics of nuclear organization.

Highlights

The spatial organization of the nucleus facilitates the interaction between distant functional elements in the genome (Tolhuis et al, 2002) and simultaneously inhibits the unwanted spatial interaction of functional elements (Dowen et al, 2014)
Compartments can be further subdivided into megabasesized genomic regions known as topologically associating domains (TADs) (Dixon et al, 2012; Nora et al, 2012), which act as regulatory scaffolds and are demarcated by binding sites of the architectural protein CTCF
It becomes apparent that the A/B compartments are further subdivided into TADs, which we identified using CatCH (Zhan et al, 2017)

Summary

Introduction

The spatial organization of the nucleus facilitates the interaction between distant functional elements in the genome (Tolhuis et al, 2002) and simultaneously inhibits the unwanted spatial interaction of functional elements (Dowen et al, 2014). Chromosomes separate active and inactive chromatin into A and B compartments, respectively. Compartments can be further subdivided into megabasesized genomic regions known as topologically associating domains (TADs) (Dixon et al, 2012; Nora et al, 2012), which act as regulatory scaffolds and are demarcated by binding sites of the architectural protein CTCF. Disruption of TAD boundaries results in the establishment of novel inter-TAD interactions. These have been shown to be associated with misexpression of Hox genes (Narendra et al, 2015), upregulation of protooncogenes (Flavahan et al, 2016), and developmental disorders (Lupian ̃ ez et al, 2015). Despite the strong links between nuclear organization and gene expression, it remains unclear how TADs, loops, and compartments contribute to gene regulation, both in steady state and throughout development

Methods

Results

Discussion

Conclusion