論文 - 詳細
| RRC ID | 59716 |
|---|---|
| 著者 | Hyle J, Zhang Y, Wright S, Xu B, Shao Y, Easton J, Tian L, Feng R, Xu P, Li C. |
| タイトル | Acute depletion of CTCF directly affects MYC regulation through loss of enhancer-promoter looping. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
Numerous pieces of evidence support the complex, 3D spatial organization of the genome dictates gene expression. CTCF is essential to define topologically associated domain boundaries and to facilitate the formation of insulated chromatin loop structures. To understand CTCF's direct role in global transcriptional regulation, we integrated the miniAID-mClover3 cassette to the endogenous CTCF locus in a human pediatric B-ALL cell line, SEM, and an immortal erythroid precursor cell line, HUDEP-2, to allow for acute depletion of CTCF protein by the auxin-inducible degron system. In SEM cells, CTCF loss notably disrupted intra-TAD loops and TAD integrity in concurrence with a reduction in CTCF-binding affinity, while showing no perturbation to nuclear compartment integrity. Strikingly, the overall effect of CTCF's loss on transcription was minimal. Whole transcriptome analysis showed hundreds of genes differentially expressed in CTCF-depleted cells, among which MYC and a number of MYC target genes were specifically downregulated. Mechanically, acute depletion of CTCF disrupted the direct interaction between the MYC promoter and its distal enhancer cluster residing ∼1.8 Mb downstream. Notably, MYC expression was not profoundly affected upon CTCF loss in HUDEP-2 cells suggesting that CTCF could play a B-ALL cell line specific role in maintaining MYC expression. |
| 巻・号 | 47(13) |
| ページ | 6699-6713 |
| 公開日 | 2019-7-26 |
| DOI | 10.1093/nar/gkz462 |
| PII | 5498628 |
| PMID | 31127282 |
| PMC | PMC6648894 |
| MeSH | CCCTC-Binding Factor / deficiency CCCTC-Binding Factor / physiology* Cell Line, Tumor Cell Nucleus / metabolism Cell Nucleus / ultrastructure Chromatin / genetics Chromatin / ultrastructure* Down-Regulation Enhancer Elements, Genetic / genetics* Erythroid Precursor Cells / metabolism Gene Expression Regulation, Leukemic* Gene Knock-In Techniques Genes, Reporter Genes, myc* Humans Nucleic Acid Conformation Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology Promoter Regions, Genetic / genetics* Proto-Oncogene Proteins c-myc / biosynthesis* Transcriptome |
| IF | 11.147 |
| 引用数 | 7 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |