MAE-seq refines regulatory elements across the genome
文献类型: 外文期刊
第一作者: Zhu, Xiusheng
作者: Zhu, Xiusheng;Huang, Qitong;Huang, Lei;Luo, Jing;Li, Qing;Kong, Dashuai;Deng, Biao;Gu, Yi;Wang, Xueyan;Li, Chenying;Kong, Siyuan;Zhang, Yubo;Huang, Qitong;Zhang, Yubo
作者机构:
期刊名称:NUCLEIC ACIDS RESEARCH ( 影响因子:14.9; 五年影响因子:16.4 )
ISSN: 0305-1048
年卷期: 2023 年
页码:
收录情况: SCI
摘要: Proper cell fate determination relies on precise spatial and temporal genome-wide cooperation between regulatory elements (REs) and their targeted genes. However, the lengths of REs defined using different methods vary, which indicates that there is sequence redundancy and that the context of the genome may be unintelligible. We developed a method called MAE-seq (Massive Active Enhancers by Sequencing) to experimentally identify functional REs at a 25-bp scale. In this study, MAE-seq was used to identify 626879, 541617 and 554826 25-bp enhancers in mouse embryonic stem cells (mESCs), C2C12 and HEK 293T, respectively. Using similar to 1.6 trillion 25 bp DNA fragments and screening 12 billion cells, we identified 626879 as active enhancers in mESCs as an example. Comparative analysis revealed that most of the histone modification datasets were annotated by MAE-Seq loci. Furthermore, 33.85% (212195) of the identified enhancers were identified as de novo ones with no epigenetic modification. Intriguingly, distinct chromatin states dictate the requirement for dissimilar cofactors in governing novel and known enhancers. Validation results show that these 25-bp sequences could act as a functional unit, which shows identical or similar expression patterns as the previously defined larger elements, Enhanced resolution facilitated the identification of numerous cell-specific enhancers and their accurate annotation as super enhancers. Moreover, we characterized novel elements capable of augmenting gene activity. By integrating with high-resolution Hi-C data, over 55.64% of novel elements may have a distal association with different targeted genes. For example, we found that the Cdh1 gene interacts with one novel and two known REs in mESCs. The biological effects of these interactions were investigated using CRISPR-Cas9, revealing their role in coordinating Cdh1 gene expression and mESC proliferation. Our study presents an experimental approach to refine the REs at 25-bp resolution, advancing the precision of genome annotation and unveiling the underlying genome context. This novel approach not only advances our understanding of gene regulation but also opens avenues for comprehensive exploration of the genomic landscape. Graphical Abstract
分类号:
- 相关文献
作者其他论文 更多>>
-
Simultaneous change of microworld and biofilm formation in constructed wetlands filled with biochar
作者:Zhong, Hui;Jiang, Chunli;He, Xi;He, Jinke;Zhao, Yaqi;Chen, Yucheng;Huang, Lei;Zhong, Hui;Jiang, Chunli;He, Xi;He, Jinke;Zhao, Yaqi;Chen, Yucheng;Huang, Lei;Huang, Lei;Huang, Lei
关键词:Constructed wetland; Biochar; Biofilm; Extracellular polymeric substance; Extracellular protein
-
Cryoprotective effect of fistular onion stalk polysaccharide on frozen surimi derived from bighead carp: Physicochemical properties and gel quality during storage
作者:Sun, Xiaoyue;Li, Qing;Ding, Ning;Liang, Shijie;Mubango, Elliot;Yu, Qinye;Dai, Ruitong;Tan, Yuqing;Luo, Yongkang;Hong, Hui;Zheng, Yanyan;Hong, Hui
关键词:Bighead carp surimi; Fistular onion stalk polysaccharide; Frozen storage; Cryoprotectant; Gel properties; Protein denaturation
-
Single-cell omics: A new direction for functional genetic research in human diseases and animal models
作者:Kong, Siyuan;Li, Rongrong;Tian, Yunhan;Zhang, Yaqiu;Lu, Yuhui;Ou, Qiaoer;Gao, Peiwen;Li, Kui;Zhang, Yubo;Kong, Siyuan;Tian, Yunhan;Li, Kui;Zhang, Yubo;Zhang, Yubo
关键词:single-cell omics; multi-omics integration; human disease; cell lines; animal disease models
-
A multi-omics integrative network map of maize
作者:Han, Linqian;Zhong, Wanshun;Qian, Jia;Jin, Minliang;Tian, Peng;Zhu, Wanchao;Sun, Yonghao;Feng, Jia-Wu;Chen, Guo;Farid, Babar;Li, Ruonan;Xiong, Zimo;Li, Juan;Luo, Zi;Du, Dengxiang;Chen, Sijia;Jin, Qixiao;Li, Jiaxin;Li, Zhao;Liang, Yan;Jin, Xiaomeng;Peng, Yong;Zheng, Chang;Chen, Ling-Ling;Li, Qing;Yan, Jianbing;Yang, Fang;Li, Lin;Han, Linqian;Zhong, Wanshun;Qian, Jia;Jin, Minliang;Tian, Peng;Zhu, Wanchao;Sun, Yonghao;Li, Juan;Luo, Zi;Jin, Qixiao;Li, Zhao;Li, Qing;Yan, Jianbing;Yang, Fang;Li, Lin;Zhang, Hongwei;Liu, Xiangguo;Ye, Xinnan;Yin, Yuejia;Chen, Guo;Farid, Babar;Tian, Zhihui;Chen, Hong;Li, Weifu
关键词:
-
A novel active transposon creates allelic variation through altered translation rate to influence protein abundance
作者:Chen, Guo;Wang, Ruilin;Jiang, Yizhe;Dong, Xiaoxiao;Xu, Jing;Xu, Qiang;Kan, Qiuxin;Luo, Zhixiang;Li, Qing;Chen, Guo;Springer, Nathan M.;Li, Qing
关键词:
-
Characterization of Gut Microbiota Compositions along the Intestinal Tract in CD163/pAPN Double Knockout Piglets and Their Potential Roles in Iron Absorption
作者:Zhang, Xiu-Ling;Xu, Kui;Xu, Chang-Jiang;Che, Jing-Jing;Liu, Zhi-Guo;Wang, Bing-Yuan;Mu, Yu-Lian;Li, Kui;Zhang, Xiu-Ling;Zhou, Yan-Rong;Xu, Si;Xiong, Yu-Jian;Xiao, Shao-Bo;Zhou, Yan-Rong;Xu, Si;Xiong, Yu-Jian;Xiao, Shao-Bo;Xu, Song-Song;Huang, Lei;Li, Kui
关键词:16S rRNA; iron absorption; gut microbiota; piglet; carboxylic acids
-
Specific colorimetric detection of methylmercury based on peroxidase-like activity regulation of carbon dots/Au NPs nanozyme
作者:Li, Qiulan;Li, Hong;Li, Kexiang;Gu, Yi;Wang, Yijie;Yang, Dezhi;Yang, Yaling;Yang, Dezhi;Li, Hong;Gao, Lei
关键词:Methylmercury; Nanozyme; Gold amalgamation; Peroxidase-like activity; Colorimetric