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Mol Cell 2017 Mar 02;655:873-884.e8. doi: 10.1016/j.molcel.2017.01.030.
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Gene Resistance to Transcriptional Reprogramming following Nuclear Transfer Is Directly Mediated by Multiple Chromatin-Repressive Pathways.

Jullien J , Vodnala M , Pasque V , Oikawa M , Miyamoto K , Allen G , David SA , Brochard V , Wang S , Bradshaw C , Koseki H , Sartorelli V , Beaujean N , Gurdon J .

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

PubMed ID: 28257702
PMC ID: PMC5344684
Article link: Mol Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: dnmt1 h2ac21 kdm6b otx2 prc1 sox2 trap1 usp21
Antibodies: H3f3a Ab15 HA Ab10 HA Ab11 HIST1H2AA Ab1 HIST1H3A Ab1 Hist1H3A Ab2

GEO Series: GSE87872: NCBI

Article Images: [+] show captions
References [+] :
Agger, UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. 2007, Pubmed