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Selective identification of epigenetic regulators at methylated genomic sites by SelectID

Wenchang Qian, Penglei Jiang, Mingming Niu, Yujuan Fu, Deyu Huang, Dong Zhang, Ying Liang, Qiwei Wang, Yingli Han, Xin Zeng, Yixin Shi, Lingli Jiang, Zebin Yu, Jinxin Li, Huan Lu, Hong Wang (), Baohui Chen () and Pengxu Qian ()
Additional contact information
Wenchang Qian: State Key Laboratory of Experimental Hematology
Penglei Jiang: State Key Laboratory of Experimental Hematology
Mingming Niu: Chinese Academy of Medical Sciences & Peking Union Medical College
Yujuan Fu: Zhejiang University School of Medicine
Deyu Huang: State Key Laboratory of Experimental Hematology
Dong Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Ying Liang: Zhejiang University School of Medicine
Qiwei Wang: State Key Laboratory of Experimental Hematology
Yingli Han: State Key Laboratory of Experimental Hematology
Xin Zeng: State Key Laboratory of Experimental Hematology
Yixin Shi: State Key Laboratory of Experimental Hematology
Lingli Jiang: State Key Laboratory of Experimental Hematology
Zebin Yu: State Key Laboratory of Experimental Hematology
Jinxin Li: State Key Laboratory of Experimental Hematology
Huan Lu: State Key Laboratory of Experimental Hematology
Hong Wang: Chinese Academy of Medical Sciences & Peking Union Medical College
Baohui Chen: Zhejiang University School of Medicine
Pengxu Qian: State Key Laboratory of Experimental Hematology

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract DNA methylation is a significant component in proximal chromatin regulation and plays crucial roles in regulating gene expression and maintaining the repressive state of retrotransposon elements. However, accurate profiling of the proteomics which simultaneously identifies specific DNA sequences and their associated epigenetic modifications remains a challenge. Here, we report a strategy termed SelectID (selective profiling of epigenetic control at genome targets identified by dCas9), which introduces methylated DNA binding domain into dCas9-mediated proximity labeling system to enable in situ protein capture at repetitive elements with 5-methylcytosine (5mC) modifications. SelectID is demonstrated as feasible as dCas9-TurboID system at specific DNA methylation regions, such as the chromosome 9 satellite. Using SelectID, we successfully identify CHD4 as potential repressors of methylated long interspersed nuclear element-1 (LINE-1) retrotransposon through direct binding at the 5’ untranslated region (5’UTR) of young LINE-1 elements. Overall, our SelectID approach has opened up avenues for uncovering potential regulators of specific DNA regions with DNA methylation, which will greatly facilitate future studies on epigenetic regulation.

Date: 2025
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DOI: 10.1038/s41467-025-59002-y

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