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Series GSE218232 Query DataSets for GSE218232
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.
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;
Contributor(s) Qin K, Blobel GA
Citation(s) 36893455
Submission date Nov 17, 2022
Last update date May 31, 2023
Contact name KUNHUA QIN
Phone 2153603146
Organization name Children's Hospital of Philadelphia
Lab Gerd A Blobel
Street address 3615 Civic Center Blvd, 315H
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (23)
GSM6737601 Neg2 rep1_HUDEP-2 cells
GSM6737602 BMI1 g1 rep1_HUDEP-2 cells
GSM6737603 BMI1 g2 rep1_HUDEP-2 cells
This SubSeries is part of SuperSeries:
GSE218233 Molecular Dissection of Polycomb Group Protein-mediated Fetal Hemoglobin Repression
BioProject PRJNA902782

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Supplementary file Size Download File type/resource
GSE218232_RAW.tar 35.1 Mb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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