| 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
|
| リソース情報 |
| ヒト・動物細胞 |
HUDEP-2(RCB4557) |
