|
| Status |
Public on Feb 05, 2024 |
| Title |
Let-7 miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The fetal hemoglobin (HBG) regulator BCL11A is repressed by HIC2 to regulate hemoglobin switching. HIC2 itself is under developmental control, highly expressed in fetal tissues and decreased in adult cells, but the mechanism of this developmental regulation is unclear. Here, we demonstrate that HIC2 is developmentally controlled by miRNAs, and loss of global miRNA biogenesis through DICER1 depletion leads to upregulation of HIC2 and HBG. We subsequently identify the adult-expressed let-7 miRNA family as a repressor of HIC2 expression. Ectopic expression of let-7 in fetal-type cells repressed HIC2 levels, while let-7 inhibition in adult erythroblasts upregulated HIC2 levels. Let-7 regulates BCL11A and HBG through induction of HIC2 and reduction of GATA1 binding at the BCL11A erythroid enhancer. Finally, HIC2 depletion rescues BCL11A-mediated repression of fetal hemoglobin in let-7 inhibited cells. Together these data demonstrate a key miRNA-mediated mechanism for developmental regulation of BCL11A expression and fetal hemoglobin repression in adult erythroid cells.
|
| |
|
| Overall design |
Experiments were performed with 2 replicates from independent donors. Scramble samples were used as controls.
|
| |
|
| Contributor(s) |
Huang P |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Oct 20, 2022 |
| Last update date |
Feb 06, 2024 |
| Contact name |
Peng Huang |
| E-mail(s) |
waliays@gmail.com
|
| Organization name |
Guangzhou Medical University
|
| Department |
GMU-GIBH Joint School of Life Sciences
|
| Lab |
Peng Huang
|
| Street address |
Xinzao, Panyu District
|
| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
511436 |
| Country |
China |
| |
|
| Platforms (1) |
|
| Samples (10)
|
|
| This SubSeries is part of SuperSeries: |
| GSE216197 |
Let-7 miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching |
|
| Relations |
| BioProject |
PRJNA892547 |
Less...
More...