Author
Listed:
- Shuyan Ji
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Fengling Chen
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Paula Stein
(National Institutes of Health
University of Pennsylvania)
- Jiacheng Wang
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Ziming Zhou
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Lijuan Wang
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Qing Zhao
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Zili Lin
(Tsinghua University
Tsinghua-Peking Center for Life Sciences
Beijing University of Agriculture)
- Bofeng Liu
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Kai Xu
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Fangnong Lai
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Zhuqing Xiong
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Xiaoyu Hu
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Tianxiang Kong
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Feng Kong
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Bo Huang
(Zhejiang University School of Medicine)
- Qiujun Wang
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Qianhua Xu
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Qiang Fan
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Ling Liu
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
- Carmen J. Williams
(National Institutes of Health)
- Richard M. Schultz
(University of Pennsylvania
Physiology and Cell Biology School of Veterinary Medicine University of California, Davis)
- Wei Xie
(Tsinghua University
Tsinghua-Peking Center for Life Sciences)
Abstract
Zygotic genome activation (ZGA) activates the quiescent genome to enable the maternal-to-zygotic transition1,2. However, the identity of transcription factors that underlie mammalian ZGA in vivo remains elusive. Here we show that OBOX, a PRD-like homeobox domain transcription factor family (OBOX1–OBOX8)3–5, are key regulators of mouse ZGA. Mice deficient for maternally transcribed Obox1/2/5/7 and zygotically expressed Obox3/4 had a two-cell to four-cell arrest, accompanied by impaired ZGA. The Obox knockout defects could be rescued by restoring either maternal and zygotic OBOX, which suggests that maternal and zygotic OBOX redundantly support embryonic development. Chromatin-binding analysis showed that Obox knockout preferentially affected OBOX-binding targets. Mechanistically, OBOX facilitated the ‘preconfiguration’ of RNA polymerase II, as the polymerase relocated from the initial one-cell binding targets to ZGA gene promoters and distal enhancers. Impaired polymerase II preconfiguration in Obox mutants was accompanied by defective ZGA and chromatin accessibility transition, as well as aberrant activation of one-cell polymerase II targets. Finally, ectopic expression of OBOX activated ZGA genes and MERVL repeats in mouse embryonic stem cells. These data thus demonstrate that OBOX regulates mouse ZGA and early embryogenesis.
Suggested Citation
Shuyan Ji & Fengling Chen & Paula Stein & Jiacheng Wang & Ziming Zhou & Lijuan Wang & Qing Zhao & Zili Lin & Bofeng Liu & Kai Xu & Fangnong Lai & Zhuqing Xiong & Xiaoyu Hu & Tianxiang Kong & Feng Kong, 2023.
"OBOX regulates mouse zygotic genome activation and early development,"
Nature, Nature, vol. 620(7976), pages 1047-1053, August.
Handle:
RePEc:nat:nature:v:620:y:2023:i:7976:d:10.1038_s41586-023-06428-3
DOI: 10.1038/s41586-023-06428-3
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Cited by:
- Mujahid Ali & Lubna Younas & Jing Liu & Huangyi He & Xinpei Zhang & Qi Zhou, 2024.
"Development and evolution of Drosophila chromatin landscape in a 3D genome context,"
Nature Communications, Nature, vol. 15(1), pages 1-15, December.
- Jiajun Tan & Yingfeng Li & Xiang Li & Xiaoxiao Zhu & Liping Liu & Hua Huang & Jiahua Wei & Hailing Wang & Yong Tian & Zhigao Wang & Zhuqiang Zhang & Bing Zhu, 2024.
"Pramel15 facilitates zygotic nuclear DNMT1 degradation and DNA demethylation,"
Nature Communications, Nature, vol. 15(1), pages 1-17, December.
- Ya Gao & Daisylyn Senna Tan & Mathias Girbig & Haoqing Hu & Xiaomin Zhou & Qianwen Xie & Shi Wing Yeung & Kin Shing Lee & Sik Yin Ho & Vlad Cojocaru & Jian Yan & Georg K. A. Hochberg & Alex Mendoza & , 2024.
"The emergence of Sox and POU transcription factors predates the origins of animal stem cells,"
Nature Communications, Nature, vol. 15(1), pages 1-16, December.
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