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| 1 | Potential application of FoldX force field based protein modeling in zinc finger nucleases design显示文摘Engineered sequence-specific zinc finger nucleases (ZFNs) make the highly efficient modification of eukaryotic genomes possible.However,most current strategies for developing zinc finger nucleases with customized sequence specificities require the construction of numerous tandem arrays of zinc finger proteins (ZFPs),and subsequent largescale in vitro validation of their DNA binding affinities and specificities via bacterial selection.The labor and expertise required in this complex process limits the broad adoption of ZFN technology.An effective computational assisted design strategy will lower the complexity of the production of a pair of functional ZFNs.Here we used the FoldX force field to build 3D models of 420 ZFP-DNA complexes based on zinc finger arrays developed by the Zinc Finger Consortium using OPEN (oligomerized pool engineering).Using nonlinear and linear regression analysis,we found that the calculated protein-DNA binding energy in a modeled ZFP-DNA complex strongly correlates to the failure rate of the zinc finger array to show significant ZFN activity in human cells.In our models,less than 5% of the three-finger arrays with calculated protein-DNA binding energies lower than 13.132 kcal mol 1 fail to form active ZFNs in human cells.By contrast,for arrays with calculated protein-DNA binding energies higher than 5 kcal mol 1,as many as 40% lacked ZFN activity in human cells.Therefore,we suggest that the FoldX force field can be useful in reducing the failure rate and increasing efficiency in the design of ZFNs. | HE ZuYong MEI Gui ZHAO ChunPeng CHEN YaoSheng | 2011 | Science China(Life Sciences)2011，54，5： | 2 |
| 2 | Comparison of the longissimus muscle proteome between obese and lean pigs at 180 days显示文摘 | Anning Li Delin Mo Xiao Zhao Wei Jiang Peiqing Cong Zuyong He Shuqi Xiao Xiaohong Liu Yaosheng Chen | 2013 | Mammalian Genome2013，，1： | 1 |
| 3 | Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs显示文摘Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thickness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) pigs.Results We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing. | Tianqi Duo Xiaohong Liu Delin Mo Yu Bian Shufang Cai Min Wang Ruiqiang Li Qi Zhu Xian Tong Ziyun Liang Weilun Jiang Shiyi Chen Yaosheng Chen Zuyong He | 2024 | Journal of Animal Science and Biotechnology2024，15，1： | 0 |
| 4 | The structure-based design of zinc finger nucleases can facilitate genomic editing显示文摘A recent study of significant research value carried out at the State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, | ZuYong He Gui Mei ChunPeng Zhao YaoSheng Chen | 2011 | Chinese Science Bulletin2011，56，21： | 0 |
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