論文 - 詳細
| RRC ID | 64367 |
|---|---|
| 著者 | Qi Q, Cheng L, Tang X, He Y, Li Y, Yee T, Shrestha D, Feng R, Xu P, Zhou X, Pruett-Miller S, Hardison RC, Weiss MJ, Cheng Y. |
| タイトル | Dynamic CTCF binding directly mediates interactions among cis-regulatory elements essential for hematopoiesis. |
| ジャーナル | Blood |
| Abstract |
While constitutive CCCTC-binding factor (CTCF)-binding sites are needed to maintain relatively invariant chromatin structures, such as topologically associating domains, the precise roles of CTCF to control cell-type-specific transcriptional regulation remain poorly explored. We examined CTCF occupancy in different types of primary blood cells derived from the same donor to elucidate a new role for CTCF in gene regulation during blood cell development. We identified dynamic, cell-type-specific binding sites for CTCF that colocalize with lineage-specific transcription factors. These dynamic sites are enriched for single-nucleotide polymorphisms that are associated with blood cell traits in different linages, and they coincide with the key regulatory elements governing hematopoiesis. CRISPR-Cas9-based perturbation experiments demonstrated that these dynamic CTCF-binding sites play a critical role in red blood cell development. Furthermore, precise deletion of CTCF-binding motifs in dynamic sites abolished interactions of erythroid genes, such as RBM38, with their associated enhancers and led to abnormal erythropoiesis. These results suggest a novel, cell-type-specific function for CTCF in which it may serve to facilitate interaction of distal regulatory emblements with target promoters. Our study of the dynamic, cell-type-specific binding and function of CTCF provides new insights into transcriptional regulation during hematopoiesis. |
| 巻・号 | 137(10) |
| ページ | 1327-1339 |
| 公開日 | 2021-3-11 |
| DOI | 10.1182/blood.2020005780 |
| PII | S0006-4971(21)00546-2 |
| PMID | 33512425 |
| PMC | PMC7955410 |
| MeSH | Binding Sites CCCTC-Binding Factor / metabolism* Cell Line Cells, Cultured Enhancer Elements, Genetic Erythroid Cells / cytology Erythroid Cells / metabolism Erythropoiesis* Humans Promoter Regions, Genetic Protein Binding RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism Regulatory Elements, Transcriptional* Transcriptional Activation |
| IF | 17.794 |
| 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 | 6 |
| 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) |