Selective identification of epigenetic regulators at methylated genomic sites by SelectID
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.
Authors
- Pengxu Qian (ORCID: https://orcid.org/0000-0001-5636-6704)
- Yingli Han (ORCID: https://orcid.org/0000-0003-3421-0965)
- Baohui Chen (ORCID: https://orcid.org/0000-0002-8999-6531)
- Penglei Jiang (ORCID: https://orcid.org/0000-0002-5518-7437)
- Yujuan Fu (ORCID: https://orcid.org/0000-0002-6709-1539)
- Mingming Niu (ORCID: https://orcid.org/0000-0002-4930-3745)
- Wenchang Qian (ORCID: https://orcid.org/0000-0001-5257-731X)
- Huan Lu (ORCID: https://orcid.org/0000-0003-4425-5454)
- Zebin Yu (ORCID: https://orcid.org/0000-0002-5595-355X)
- Lingli Jiang (ORCID: https://orcid.org/0009-0000-0947-5756)
- Deyu Huang (ORCID: https://orcid.org/0009-0008-0705-418X)
- David Zhang (ORCID: https://orcid.org/0000-0002-5027-5286)
- Hong Wang (ORCID: https://orcid.org/0000-0002-6215-6348)
- Ying Liang (ORCID: https://orcid.org/0000-0001-7824-5399)
- Qiwei Wang (ORCID: https://orcid.org/0000-0001-9197-3163)
- Jinxin Li (ORCID: https://orcid.org/0000-0002-7713-8564)
- Xin Zeng (ORCID: https://orcid.org/0000-0003-1014-2558)
- Yixin Shi (ORCID: https://orcid.org/0009-0000-0244-9838)
Institutions
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Tianjin Anding Hospital (CN)
- Institute of Hematology & Blood Diseases Hospital (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-18
- DOI
- https://doi.org/10.1038/s41467-025-59002-y
- Citations
- 6
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 4.84
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Zhejiang University
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities
- Natural Science Foundation of Zhejiang Province