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Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells
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
Abstract:
...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.
PMID: 33357405
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