RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2021 
FD June 01 
VO 31 
IS 6 
SP 968 
OP 980 
DO 10.1101/gr.269951.120 
UL http://genome.cshlp.org/content/31/6/968.abstract 
AB 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.