Reprogramming of three-dimensional chromatin organization in the early embryo

Abstract

Chromatin organization within the three-dimensional (3D) nuclear space is important for proper gene expression and developmental programming. This organization is established during the dramatic reprogramming that occurs in early embryonic development. Thus, the early embryo is an ideal model for examining the formation and dynamics of 3D chromatin structure. Advances in high-resolution microscopy and single-nucleus genomic analyses have provided fundamental insights into the mechanisms driving genome organization in the early embryo. Here, we highlight recent findings describing the dynamics and driving mechanisms for establishing 3D chromatin organization and discuss the role such organization has on gene regulation in early embryonic development.

Figure 1.. 3D chromatin structure is reorganized over early development.

(a) Summary of initiation and progression of ZGA (indicated by gray gradient) in fruit flies (Drosophila), frogs (Xenopus), zebrafish, mice and humans. (b) TADs are established concomitantly with ZGA. (c) A/B compartmentalization is evident pre-ZGA in mice but occurs during ZGA in Drosophila and after ZGA in frogs, zebrafish, and humans. (d) Heterochromatin (indicated by condensation of HP1a) is gradually formed over the MZT.

Figure 2.. Chromosomes are organized at multiple levels.

(a) Representative linear diagram of TAD structure showing contact frequencies that would be identified by Micro-C or Hi-C. Relative locations of enhancers, promoters, and tethering elements with insulator-binding proteins and pioneer factors are indicated. (b) Representative model of the chromatin architecture depicted in (a). High-concentration hub formation by tethering-element bound pioneer factors may facilitate enhancer-promoter interactions. TAD boundaries largely function to inhibit non-specific interactions between regulatory regions.