Gene Resistance to Transcriptional Reprogramming following Nuclear Transfer Is Directly Mediated by Multiple Chromatin-Repressive Pathways

• DOI: 10.1016/j.molcel.2017.01.030
• Publication Date: 2017-03-02T19:29:08Z
• Authors: Jerome Jullien; Munender Vodnala; Vincent Pasque; Mami Oikawa; Kei Miyamoto; George Allen; Sarah Anne David; Vincent Brochard; Stan Wang; Charles Bradshaw; Haruhiko Koseki; Vittorio Sartorelli; Nathalie Beaujean; John Gurdon
• Keywords: Reprogramming

Understanding the mechanism of resistance genes to reactivation will help improve success nuclear reprogramming. Using mouse embryonic fibroblast nuclei with normal or reduced DNA methylation in combination chromatin modifiers able erase H3K9me3, H3K27me3, and H2AK119ub1 from transplanted nuclei, we reveal basis for transcriptional reprogramming by oocyte factors. A majority is affected more than one type treatment, suggesting that can require repression through multiple epigenetic mechanisms. We classify resistant according their sensitivity 11 modifier combinations, revealing existence synergistic as well adverse effects on removal resistance. further demonstrate USP21 reduces its H2AK119 deubiquitylation activity. Finally, provide evidence H2A ubiquitylation also contributes transfer embryos.