151. Genome-Scale CRISPR-Cas12a Screen Identifies Novel Fetal Hemoglobin Regulators
- Author
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Traxler, Elizabeth A., Komar, Chad, Saari, Megan, Thrasher, A Josephine, Qin, Kunhua, Khandros, Eugene, Hotan, Quynn, Abdulmalik, Osheiza, Shao, Claire, Chen, Qingzhou, Minn, Andy J., Keller, Cheryl A., Shi, Junwei, and Blobel, Gerd A.
- Abstract
Reversal of the postnatal hemoglobin switch in red blood cells is a promising approach to therapies for sickle cell disease and β-thalassemia, as reactivating fetal hemoglobin (HbF, α2γ2) in adult red blood cells ameliorates disease complications. Studies over several decades have illuminated the paradigm of this fetal-to-adult hemoglobin transition, including central roles of transcriptional repressors BCL11A, LRF, and NFIA/X, which recruit repressive chromatin modifiers to the γ-globin locus. To elucidate undescribed regulatory mechanisms of these molecules and reveal new targets for therapies, we performed the first genome-wide genetic screen to pinpoint specific pathways or protein complexes that regulate HbF expression in adult erythroid cells.
- Published
- 2023
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