CTCF looping is established during gastrulation in medaka embryos
- Ryohei Nakamura1,13,
- Yuichi Motai2,13,
- Masahiko Kumagai3,
- Candice L. Wike4,
- Haruyo Nishiyama1,
- Yoichiro Nakatani5,
- Neva C. Durand6,7,8,9,10,
- Kaori Kondo11,
- Takashi Kondo11,
- Tatsuya Tsukahara12,
- Atsuko Shimada1,
- Bradley R. Cairns4,
- Erez Lieberman Aiden6,7,8,9,10,
- Shinichi Morishita2 and
- Hiroyuki Takeda1
- 1Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033 Japan;
- 2Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-8562, Japan;
- 3Advanced Analysis Center, National Agriculture and Food Research Organization, Tsukuba, Ibaraki 305-8602, Japan;
- 4Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA;
- 5Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan;
- 6The Center for Genome Architecture, Baylor College of Medicine, Houston, Texas 77030, USA;
- 7Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
- 8Department of Computer Science, Department of Computational and Applied Mathematics, Rice University, Houston, Texas 77005, USA;
- 9Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139 USA;
- 10Center for Theoretical Biological Physics, Rice University, Houston, Texas 77030, USA;
- 11RIKEN-IMS, Laboratory for Developmental Genetics, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan;
- 12Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
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↵13 These authors contributed equally to this work.
Abstract
Chromatin looping plays an important role in genome regulation. However, because ChIP-seq and loop-resolution Hi-C (DNA-DNA proximity ligation) are extremely challenging in mammalian early embryos, the developmental stage at which cohesin-mediated loops form remains unknown. Here, we study early development in medaka (the Japanese killifish, Oryzias latipes) at 12 time points before, during, and after gastrulation (the onset of cell differentiation) and characterize transcription, protein binding, and genome architecture. We find that gastrulation is associated with drastic changes in genome architecture, including the formation of the first loops between sites bound by the insulator protein CTCF and a large increase in the size of contact domains. In contrast, the binding of the CTCF is fixed throughout embryogenesis. Loops form long after genome-wide transcriptional activation, and long after domain formation seen in mouse embryos. These results suggest that, although loops may play a role in differentiation, they are not required for zygotic transcription. When we repeated our experiments in zebrafish, loops did not emerge until gastrulation, that is, well after zygotic genome activation. We observe that loop positions are highly conserved in synteny blocks of medaka and zebrafish, indicating that the 3D genome architecture has been maintained for >110–200 million years of evolution.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.269951.120.
- Received August 6, 2020.
- Accepted March 30, 2021.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
