2. Academic Validation
  3. Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells

Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells

  • Cell Stem Cell. 2021 Apr 1;28(4):732-747.e9. doi: 10.1016/j.stem.2020.11.018.
Rongrong Le 1,  Yixin Huang 2,  Yanping Zhang 2,  Hu Wang 3,  Jiaming Lin 2,  Yu Dong 2,  Ziyi Li 2,  Mingyue Guo 2,  Xiaochen Kou 2,  Yanhong Zhao 2,  Mo Chen 2,  Qianshu Zhu 2,  Anqi Zhao 2,  Jiqing Yin 2,  Jiatong Sun 4,  Zhongqu Su 4,  Kerong Shi 4,  Yawei Gao 2,  Jiayu Chen 2,  Wenqiang Liu 2,  Lan Kang 2,  Yixuan Wang 2,  Chong Li 2,  Xiaoyu Liu 2,  Rui Gao 2,  Hong Wang 2,  Zhenyu Ju 5,  Shaorong Gao 6
Affiliations

Affiliations

  • 1 Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Frontier Science Center for Stem Cells, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: [email protected].
  • 2 Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Frontier Science Center for Stem Cells, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
  • 3 Key Laboratory of Regenerative Medicine of Ministry of Education, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, 510632 Guangdong, China.
  • 4 College of Animal Science and Technology, Shandong Key Laboratory of Animal Bioengineering and Disease Prevention, Shandong Agricultural University, Taian, Shandong 271018, China.
  • 5 Key Laboratory of Regenerative Medicine of Ministry of Education, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, 510632 Guangdong, China. Electronic address: [email protected].
  • 6 Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Frontier Science Center for Stem Cells, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Tsingtao Advanced Research Institute, Tongji University, Qingdao 266071, China. Electronic address: [email protected].
PMID: 33357405 DOI: 10.1016/j.stem.2020.11.018
Abstract

Telomeres play vital roles in ensuring chromosome stability and are thus closely linked with the onset of aging and human disease. Telomeres undergo extensive lengthening during early embryogenesis. However, the detailed molecular mechanism of telomere resetting in early embryos remains unknown. Here, we show that DCAF11 (Ddb1- and Cul4-associated factor 11) participates in telomere elongation in early embryos and 2-cell-like embryonic stem cells (ESCs). The deletion of DCAF11 in embryos and ESCs leads to reduced telomere sister-chromatid exchange (T-SCE) and impairs telomere lengthening. Importantly, Dcaf11-deficient mice exhibit gradual telomere erosion with successive generations, and hematopoietic stem cell (HSC) activity is also greatly compromised. Mechanistically, DCAF11 targets Kap1 (KRAB-associated protein 1) for ubiquitination-mediated degradation, leading to the activation of Zscan4 downstream enhancer and the removal of heterochromatic H3K9me3 at telomere/subtelomere regions. Our study therefore demonstrates that DCAF11 plays important roles in telomere elongation in early embryos and ESCs through activating Zscan4.

Keywords

ESCs; Kap1; Zscan4; alternative lengthening of telomeres; embryo.

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