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Series GSE182530 Query DataSets for GSE182530
Status Public on May 26, 2022
Title HIC2 represses BCL11A transcription to regulate hemoglobin switching during development [CUT&RUN]
Organism Homo sapiens
Experiment type Other
Summary The switch from fetal to adult hemoglobin production has been studied in great depth in part because of its relevance to the treatment of hemolobinopathies. Transcription factor BCL11A, which is essential for repression of the fetal beta-type globin (γ-globin) genes after birth, is largely controlled at the level of transcription but the mechanism of BCL11A developmental control is unknown. Here, using a CRISPR-Cas9 screen in human erythroblasts, we identify transcription factor HIC2 as a repressor of BCL11A transcription. HIC2 and BCL11A expression are anti-correlated in fetal and adult erythroblasts. Forced expression of HIC2 in adult erythroblasts silences BCL11A transcription and markedly induces γ-globin expression. HIC2 binds selectively to constituent erythroid developmental BCL11A enhancer to reduce chromatin accessibility and impair access by transcription factor GATA1, resulting in loss of enhancer activity and enhancer-promoter contacts. Conversely, loss of HIC2 in fetal erythroblasts increases enhancer accessibility, enables GATA1 binding and induces BCL11A transcription. HIC2 is unveiled as a critical evolutionarily conserved regulator of globin gene switching by imposing developmental control on the BCL11A gene.
Overall design CD34+ cells derived from human fetal liver and peripheral blood were cultured and differentiated to erythroblasts. H3K27ac and GATA1 CUT&RUN were performed.
Contributor(s) Huang P
Citation(s) 35941187
Submission date Aug 21, 2021
Last update date Aug 25, 2022
Contact name Peng Huang
Organization name Guangzhou Medical University
Department GMU-GIBH Joint School of Life Sciences
Lab Peng Huang
Street address Xinzao, Panyu District
City Guangzhou
State/province Guangdong
ZIP/Postal code 511436
Country China
Platforms (1)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (8)
GSM5530945 Fetal_H3K27ac_r1
GSM5530946 Fetal_H3K27ac_r2
GSM5530947 Adult_H3K27ac_r1
This SubSeries is part of SuperSeries:
GSE173587 HIC2 represses BCL11A transcription to regulate hemoglobin switching during development
BioProject PRJNA756674
SRA SRP333538

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Supplementary file Size Download File type/resource
GSE182530_RAW.tar 420.8 Mb (http)(custom) TAR (of BED, BIGWIG)
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Raw data are available in SRA
Processed data provided as supplementary file

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