ArticleNucleic acids research2022
Coupling high-throughput mapping with proteomics analysis delineates cis-regulatory elements at high resolution.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- From binding to networks: methods for identifying transcription factor targets in plant systems.Frontiers in plant science · 2026Review
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- SATB2, coordinated with CUX1, regulates IL-1β-induced senescence-like phenotype in endothelial cells by fine-tuning the atherosclerosis-associated p16Aging cell · 2023Article
- Comprehensive genomics analysis of aging related gene signature to predict the prognosis and drug resistance of colon adenocarcinoma.Frontiers in pharmacology · 2023Article
- An Improved EMSA-based Method to Prioritize CandidateBio-protocol · 2022Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Growing evidence suggests that functional cis-regulatory elements (cis-REs) not only exist in epigenetically marked but also in unmarked sites of the human genome. While it is already difficult to identify cis-REs in the epigenetically marked sites, interrogating cis-REs residing within the unmarked sites is even more challenging. Here, we report adapting Reel-seq, an in vitro high-throughput (HTP) technique, to fine-map cis-REs at high resolution over a large region of the human genome in a systematic and continuous manner. Using Reel-seq, as a proof-of-principle, we identified 408 candidate cis-REs by mapping a 58 kb core region on the aging-related CDKN2A/B locus that harbors p16INK4a. By coupling Reel-seq with FREP-MS, a proteomics analysis technique, we characterized two cis-REs, one in an epigenetically marked site and the other in an epigenetically unmarked site. These elements are shown to regulate the p16INK4a expression over an ∼100 kb distance by recruiting the poly(A) binding protein PABPC1 and the transcription factor FOXC2. Downregulation of either PABPC1 or FOXC2 in human endothelial cells (ECs) can induce the p16INK4a-dependent cellular senescence. Thus, we confirmed the utility of Reel-seq and FREP-MS analyses for the systematic identification of cis-REs at high resolution over a large region of the human genome.
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