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| Status |
Public on May 26, 2022 |
| Title |
HIC2 represses BCL11A transcription to regulate hemoglobin switching during development (Capture-C) |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
The switch from fetal to adult hemoglobin production has been studied in great depth in part because of its relevance to the treatment of hemolobinopathies. Transcription factor BCL11A, which is essential for repression of the fetal beta-type globin (γ-globin) genes after birth, is largely controlled at the level of transcription but the mechanism of BCL11A developmental control is unknown. Here, using a CRISPR-Cas9 screen in human erythroblasts, we identify transcription factor HIC2 as a repressor of BCL11A transcription. HIC2 and BCL11A expression are anti-correlated in fetal and adult erythroblasts. Forced expression of HIC2 in adult erythroblasts silences BCL11A transcription and markedly induces γ-globin expression. HIC2 binds selectively to constituent erythroid developmental BCL11A enhancer to reduce chromatin accessibility and impair access by transcription factor GATA1, resulting in loss of enhancer activity and enhancer-promoter contacts. Conversely, loss of HIC2 in fetal erythroblasts increases enhancer accessibility, enables GATA1 binding and induces BCL11A transcription. HIC2 is unveiled as a critical evolutionarily conserved regulator of globin gene switching by imposing developmental control on the BCL11A gene.
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| Overall design |
HIC2 overexpression
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| |
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| Contributor(s) |
Huang P |
| Citation(s) |
35941187 |
| Submission date |
Apr 29, 2021 |
| Last update date |
Aug 25, 2022 |
| 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 |
| |
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| Platforms (1) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE173587 |
HIC2 represses BCL11A transcription to regulate hemoglobin switching during development |
|
| Relations |
| BioProject |
PRJNA726212 |
| SRA |
SRP317335 |
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