TY - JOUR A1 - Nakamura, Ryohei A1 - Motai, Yuichi A1 - Kumagai, Masahiko A1 - Wike, Candice L. A1 - Nishiyama, Haruyo A1 - Nakatani, Yoichiro A1 - Durand, Neva C. A1 - Kondo, Kaori A1 - Kondo, Takashi A1 - Tsukahara, Tatsuya A1 - Shimada, Atsuko A1 - Cairns, Bradley R. A1 - Aiden, Erez Lieberman A1 - Morishita, Shinichi A1 - Takeda, Hiroyuki T1 - CTCF looping is established during gastrulation in medaka embryos Y1 - 2021/06/01 JF - Genome Research JO - Genome Research SP - 968 EP - 980 DO - 10.1101/gr.269951.120 VL - 31 IS - 6 UR - http://genome.cshlp.org/content/31/6/968.abstract N2 - 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. ER -