Chromatin architecture transitions from zebrafish sperm through early embryogenesis

Candice L. Wike, Yixuan Guo, Mengyao Tan, Ryohei Nakamura, Dana Klatt Shaw, Noelia Díaz, Aneasha F. Whittaker-Tademy, Neva C. Durand, Erez Lieberman Aiden, Juan M. Vaquerizas, David Grunwald, Hiroyuki Takeda, Bradley R. Cairns

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Chromatin architecture mapping in 3D formats has increased our understanding of how regulatory sequences and gene expression are connected and regulated in a genome. The 3D chromatin genome shows extensive remodeling during embryonic development, and although the cleavage-stage embryos of most species lack structure before zygotic genome activation (pre-ZGA), zebrafish has been reported to have structure. Here, we aimed to determine the chromosomal architecture in paternal/sperm zebrafish gamete cells to discern whether it either resembles or informs early pre-ZGA zebrafish embryo chromatin architecture. First, we assessed the higher-order architecture through advanced low-cell in situ Hi-C. The structure of zebrafish sperm, packaged by histones, lacks topological associated domains and instead displays “hinge-like” domains of ∼150 kb that repeat every 1–2 Mbs, suggesting a condensed repeating structure resembling mitotic chromosomes. The pre-ZGA embryos lacked chromosomal structure, in contrast to prior work, and only developed structure post-ZGA. During post-ZGA, we find chromatin architecture beginning to form at small contact domains of a median length of ∼90 kb. These small contact domains are established at enhancers, including super-enhancers, and chemical inhibition of Ep300a (p300) and Crebbpa (CBP) activity, lowering histone H3K27ac, but not transcription inhibition, diminishes these contacts. Together, this study reveals hinge-like domains in histone-packaged zebrafish sperm chromatin and determines that the initial formation of high-order chromatin architecture in zebrafish embryos occurs after ZGA primarily at enhancers bearing high H3K27ac.

Original languageEnglish
Pages (from-to)981-994
Number of pages14
JournalGenome Research
Issue number6
Publication statusPublished - Jun 2021


Dive into the research topics of 'Chromatin architecture transitions from zebrafish sperm through early embryogenesis'. Together they form a unique fingerprint.

Cite this