Cell Reports (Oct 2016)
Nono, a Bivalent Domain Factor, Regulates Erk Signaling and Mouse Embryonic Stem Cell Pluripotency
- Chun Ma,
- Violetta Karwacki-Neisius,
- Haoran Tang,
- Wenjing Li,
- Zhennan Shi,
- Haolin Hu,
- Wenqi Xu,
- Zhentian Wang,
- Lingchun Kong,
- Ruitu Lv,
- Zheng Fan,
- Wenhao Zhou,
- Pengyuan Yang,
- Feizhen Wu,
- Jianbo Diao,
- Li Tan,
- Yujiang Geno Shi,
- Fei Lan,
- Yang Shi
Affiliations
- Chun Ma
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Violetta Karwacki-Neisius
- Newborn Medicine Division, Boston Children’s Hospital, Boston, MA 02115, USA
- Haoran Tang
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Wenjing Li
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Zhennan Shi
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Haolin Hu
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Wenqi Xu
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Zhentian Wang
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Lingchun Kong
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Ruitu Lv
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Zheng Fan
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Wenhao Zhou
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Pengyuan Yang
- Department of Systems Biology, Institutes of Biomedical Sciences, Fudan University, 138 Yixue Yuan Road, Shanghai 200032, China
- Feizhen Wu
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Jianbo Diao
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Li Tan
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Yujiang Geno Shi
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Fei Lan
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- Yang Shi
- Key Laboratory of Birth Defects, Children’s Hospital and Key Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 201102, China
- DOI
- https://doi.org/10.1016/j.celrep.2016.09.078
- Journal volume & issue
-
Vol. 17,
no. 4
pp. 997 – 1007
Abstract
Nono is a component of the para-speckle, which stores and processes RNA. Mouse embryonic stem cells (mESCs) lack para-speckles, leaving the function of Nono in mESCs unclear. Here, we find that Nono functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We report that Nono loss results in robust self-renewing mESCs with epigenomic and transcriptomic features resembling the 2i (GSK and Erk inhibitors)-induced “ground state.” Erk interacts with and is required for Nono localization to a subset of bivalent genes that have high levels of poised RNA polymerase. Nono loss compromises Erk activation and RNA polymerase poising at its target bivalent genes in undifferentiated mESCs, thus disrupting target gene activation and differentiation. These findings argue that Nono collaborates with Erk signaling to regulate the integrity of bivalent domains and mESC pluripotency.
Keywords
