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| Status |
Public on Dec 09, 2024 |
| Title |
BCL11A is required for normal erythropoiesis [CUT&Run] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Genetic depletion of the transcriptional repressor BCL11A in red blood cell precursors alleviates b-hemoglobinopathies by inducing the fetal g-globin genes. However, several additional erythroid genes are regulated by BCL11A and the effects of its deficiency on erythropoiesis are insufficiently described. We discovered that Cas9 disruption of the BCL11A intron 2 erythroid enhancer in CD34+ hematopoietic stem and progenitor cells (HSPCs) according to a clinically approved strategy caused impaired expansion and increased apoptosis of erythroid precursors in vitro and in vivo. Mutant colony-forming unit erythroid (CFU-e), proerythroblasts, and basophilic erythroblasts exhibited dysregulation of 94 genes (> 2-fold change, FDR < 0.05). 25 of which are likely direct targets of BCL11A. Differentially expressed genes were associated with numerous biological pathways that impact cell expansion and survival. Our findings show that BCL11A regulates additional aspects of erythropoiesis beyond g-globin gene repression.
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| Overall design |
CUT&RUN assay was performed to identify chromatin occupancy of BCL11A. Three samples with BCL11A antibody and 3 samples with control IgG antibody were analyzed.
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| Contributor(s) |
Jang Y, Feng R, Palmer LE, Cheng Y, Yen JS, Weiss MJ |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Dec 08, 2024 |
| Last update date |
Dec 10, 2024 |
| Contact name |
Lance Palmer |
| Organization name |
St. Jude Children's Research Hospital
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| Department |
Hematology
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| Street address |
262 Danny Thomas Pl
|
| City |
Memphis |
| State/province |
TN - Tennessee |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE283797 |
BCL11A is required for normal erythropoiesis |
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| Relations |
| BioProject |
PRJNA1195596 |
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