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| Status |
Public on Mar 01, 2023 |
| Title |
Molecular Dissection of Polycomb Group Protein-mediated Fetal Hemoglobin Repression [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The fetal (HbF)-to-adult (HbA) hemoglobin switch is a paradigm for developmental gene expression control with relevance to sickle cell disease and beta-thalassemia. Polycomb repressive complex (PRC) proteins regulate this switch, and an inhibitor of the EED subunit of PRC2 entered clinical trials for fetal hemoglobin activation. Yet, how PcG complexes function in this process, their target genes and relevant subunit composition are unknown. Here, we identified the PRC1 subunit BMI1 as a novel HbF repressor. We uncovered LIN28B, IGF2BP1, and IGF2BP3 as direct BMI1 targets and demonstrate that they account for the BMI1 effects. BMI1 functions as part of the canonical PRC1 (cPRC1) subcomplex as revealed by the physical and functional dissection of BMI1 protein partners. Lastly, we demonstrate that BMI1/cPRC1 acts in concert with the PRC2 to repress HbF through the same target genes. Our study illuminates how PRC silences HbF, highlighting an epigenetic mechanism involved in hemoglobin switching.
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| Overall design |
Total RNA was isolated from HUDEP2 cells of 6 or 7 days differentiation or CD34+ HSPCs of day 8 differentiation targeted with CRISPR control sgRNA or BMI1/EZH2/CBX2,4,8 sgRNAs; Transcriptome changes were analyzed by bulk RNA-seq;
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| Contributor(s) |
Qin K, Blobel GA |
| Citation(s) |
36893455 |
| |
| Submission date |
Nov 17, 2022 |
| Last update date |
May 31, 2023 |
| Contact name |
KUNHUA QIN |
| E-mail(s) |
qink@chop.edu, kunhua.qin@gmail.com
|
| Phone |
2153603146
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| Organization name |
Children's Hospital of Philadelphia
|
| Lab |
Gerd A Blobel
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| Street address |
3615 Civic Center Blvd, 315H
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
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| Samples (23)
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| This SubSeries is part of SuperSeries: |
| GSE218233 |
Molecular Dissection of Polycomb Group Protein-mediated Fetal Hemoglobin Repression |
|
| Relations |
| BioProject |
PRJNA902782 |
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