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| Status |
Public on Dec 27, 2020 |
| Title |
Epigenetic inactivation of ERF reactivates γ-globin expression in β-thalassemia [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The fetal-to-adult hemoglobin switch is regulated in a developmental stage-specific manner and reactivation of fetal hemoglobin (HbF) has therapeutic potential for β-hemoglobinopathies. Although BCL11A and ZBTB7A interact with their coregulators, reportedly mediating most γ-globin transcriptional silencing in erythroid in trans, and in cis, the molecular mechanism underlying the epigenetic dysregulation of the switch remains largely unclear. Here we showed that epigenetic inactivation of an ETS2 repressor factor (ERF) reactivates γ-globin expression during stress erythropoiesis, and ERF depletion elevates γ-globin in erythroid cells and in erythroid progenies from the edited HSPCs engrafted into immunodeficient mice. ERF represses γ-globin by directly binding to two motifs regulating HBG expression, independently of the major HbF repressors BCL11A and ZBTB7A. We further uncovered that an lncRNA, RP11-196G18.23 mediates ERF promoter hypermethylation resulting in reactivation of g-globin. Herein, the epigenetic alterations were identified as novel modulators ameliorating the severity of b-thalassemia, thus providing novel therapeutic targets for β-hemoglobinopathies.
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| Overall design |
Examination of transcription factor ERF in HUDEP-2 cells. Input DNA served as control.
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| Contributor(s) |
Bao X, Zhang X, Wang L, Wang Z, Huang J, Zhang Q, Ye Y, Liu Y, Chen D, Zuo Y, Liu Q, Huang B, Fang J, Lao J, Feng X, Li Y, Kurita R, Nakamura Y, Yu W, Ju C, Mohandas N, Li D, Zhao C, Xu X, Huang C, Mohandas N |
| Citation(s) |
33735615 |
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| Submission date |
Nov 01, 2020 |
| Last update date |
Apr 01, 2021 |
| Contact name |
Xiuqin Bao |
| E-mail(s) |
wzj1990@i.smu.edu.cn
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| Organization name |
Southern Medical University
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| Street address |
No. 1838, Guangzhou avenue north, baiyun district, Guangzhou
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| City |
Guangzhou |
| ZIP/Postal code |
510515 |
| Country |
China |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE160603 |
Epigenetic inactivation of ERF reactivates γ-globin expression in β-thalassemia |
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| Relations |
| BioProject |
PRJNA673718 |
| SRA |
SRP290735 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE160602_RAW.tar |
433.2 Mb |
(http)(custom) |
TAR (of TDF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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