論文 - 詳細
| RRC ID | 77333 |
|---|---|
| 著者 | Boontanrart MY, Schröder MS, Stehli GM, Banović M, Wyman SK, Lew RJ, Bordi M, Gowen BG, DeWitt MA, Corn JE. |
| タイトル | ATF4 Regulates MYB to Increase γ-Globin in Response to Loss of β-Globin. |
| ジャーナル | Cell Rep |
| Abstract |
β-Hemoglobinopathies can trigger rapid production of red blood cells in a process known as stress erythropoiesis. Cellular stress prompts differentiating erythroid precursors to express high levels of fetal γ-globin. However, the mechanisms underlying γ-globin production during cellular stress are still poorly defined. Here, we use CRISPR-Cas genome editing to model the stress caused by reduced levels of adult β-globin. We find that decreased β-globin is sufficient to induce robust re-expression of γ-globin, and RNA sequencing (RNA-seq) of differentiating isogenic erythroid precursors implicates ATF4 as a causal regulator of this response. ATF4 binds within the HBS1L-MYB intergenic enhancer and regulates expression of MYB, a known γ-globin regulator. Overall, the reduction of ATF4 upon β-globin knockout decreases the levels of MYB and BCL11A. Identification of ATF4 as a key regulator of globin compensation adds mechanistic insight to the poorly understood phenomenon of stress-induced globin compensation and could inform strategies to treat hemoglobinopathies. |
| 巻・号 | 32(5) |
| ページ | 107993 |
| 公開日 | 2020-8-4 |
| DOI | 10.1016/j.celrep.2020.107993 |
| PII | S2211-1247(20)30978-5 |
| PMID | 32755585 |
| MeSH | Activating Transcription Factor 4 / genetics Activating Transcription Factor 4 / metabolism* Base Sequence Cell Differentiation / genetics Cell Line DNA, Intergenic / genetics Down-Regulation / genetics Enhancer Elements, Genetic / genetics Fetal Hemoglobin / genetics Gene Expression Regulation* Hematopoietic Stem Cells / metabolism Humans Mutation / genetics Protein Binding Proto-Oncogene Proteins c-myb / genetics* Proto-Oncogene Proteins c-myb / metabolism Repressor Proteins / metabolism Time Factors Transcription, Genetic Transcriptome / genetics Up-Regulation / genetics beta-Globins / metabolism* gamma-Globins / genetics* gamma-Globins / metabolism |
| IF | 8.109 |
| 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 | 28 |
| 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) HUDEP-1(RCB4556) |