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Series GSE103445 Query DataSets for GSE103445
Status Public on Jan 29, 2018
Title Natural regulatory mutations elevate fetal globin via disruption of BCL11A or ZBTB7A binding
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary B-hemoglobinopathies such as Sickle Cell Disease (SCD) and b-thalassemia result from mutations in the adult b-globin gene. Reactivating the developmentally silenced fetal g-globin gene is a therapeutic goal for treating SCD and b-thalassemia1. Some forms of Hereditary Persistence of Fetal Hemoglobin (HPFH), a rare benign condition in which individuals express g‑globin throughout adulthood, are caused by point mutations in the g‑globin gene promoter at regions residing ~115 and 200 base pairs upstream of the transcription start site. Here we show that the major fetal globin repressors BCL11A and ZBTB7A/LRF directly bind to the -115 and ‑200 sites, respectively. Furthermore, introduction of naturally occurring HPFH mutations into erythroid cells by CRISPR/Cas9 disrupts repressor binding and raises g‑globin expression. These findings resolve the mystery surrounding how these HPFH mutations operate and demonstrate that BCL11A and ZBTB7A/LRF are major direct repressors of the fetal globin gene.
Overall design ChIP-seq experiments were performed in two different cell lines, HUDEP-2 and K562 against BCL11A and ZBTB7A. Input samples were used as control.
Contributor(s) Martyn GE, Wienert B, Yang L, Shah M, Norton LJ, Burdach J, Kurita R, Nakamura Y, Pearson RC, Funnell AP, Quinlan KG, Crossley M
Citation(s) 29610478
Submission date Sep 05, 2017
Last update date May 15, 2019
Contact name Merlin Crossley
Organization name University of New South Wales
Department BABS
Street address UNSW
City Sydney
State/province NSW
ZIP/Postal code 2052
Country Australia
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (16)
GSM2771529 HUDEP2 BCL11A-ER-V5 ChIP-seq Rep 1
GSM2771530 HUDEP2 BCL11A-ER-V5 ChIP-seq Rep 2
GSM2771531 HUDEP2 BCL11A-ER-V5 ChIP-seq Input 1
BioProject PRJNA401837
SRA SRP116907

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE103445_HUDEP2_BCL11A_optimal_idr_peaks.bed.gz 170.8 Kb (ftp)(http) BED
GSE103445_K562_ZBTB7A_optimal_idr_peaks.bed.gz 166.3 Kb (ftp)(http) BED
GSE103445_RAW.tar 4.9 Gb (http)(custom) TAR (of BEDGRAPH, TXT)
GSE103445_hg38_modified_chr11.genome.gz 4.7 Mb (ftp)(http) GENOME
GSE103445_hg38_modified_chr11_genome.fa.gz 937.6 Mb (ftp)(http) FA
GSE103445_hg38refGene_modified_chr11.txt.gz 4.7 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file

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