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Series GSE218231 Query DataSets for GSE218231
Status Public on Mar 01, 2023
Title Molecular Dissection of Polycomb Group Protein-mediated Fetal Hemoglobin Repression [CUT&RUN]
Organism Homo sapiens
Experiment type Genome binding/occupancy 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 Chromatin occupancies of BMI1, EZH2, RING1B, CBX2, CBX4, CBX7, CBX7, and CBX8 and genomic enrichment of H3K27me3, H3K4me3, H3K27Ac, and H2AK119ub1 in HUDEP2 and primary erythroblasts were analyzed by CUT&RUN or ChIP-seq
 
Contributor(s) Qin K, Blobel GA
Citation(s) 36893455
Submission date Nov 17, 2022
Last update date Mar 18, 2023
Contact name KUNHUA QIN
E-mail(s) qink@chop.edu, kunhua.qin@gmail.com
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 (41)
GSM6737560 CUTRUN_3938_Primary Erythroblasts derived from Adult perpheral blood CD34+ donor #3905_BMI1_no treatment
GSM6737561 CUTRUN_4083_HUDEP2_BMI1_neg gRNA transduction
GSM6737562 CUTRUN_4034_HUDEP2_BMI1_Cas9 BMI gRNA #1 transduction
This SubSeries is part of SuperSeries:
GSE218233 Molecular Dissection of Polycomb Group Protein-mediated Fetal Hemoglobin Repression
Relations
BioProject PRJNA902781

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE218231_RAW.tar 5.0 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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