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Series GSE52637 Query DataSets for GSE52637
Status Public on Jul 24, 2014
Title HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Genetic studies have identified common variants within the HBS1L-MYB intergenic region on chromosome 6q associated with elevated fetal hemoglobin (HbF) levels and other clinically important human erythroid traits. The mechanism by which the non-coding sequence variants affect these traits is still not clear. Here we report that several of the variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. We show that several of the variants reduce transcription factor binding, affecting long-range interactions with MYB, and MYB expression levels. We provide here a functional explanation for the genetic association of HBS1L-MYB intergenic polymorphisms with human erythroid traits and HbF levels. Our results further designate MYB as a bona fide target for therapeutic induction of HbF to ameliorate sickle cell and β-thalassemia disease severity.
Overall design ChIP-Sequencing profiles of the LDB1 and CTCF proteins were generated using primary human erythroid progenitors. 3C-Seq experiments (in duplicate, primary human erythroid progenitors) were performed using the MYB promoter and the -84kb upstream enhancer as viewpoints.
Contributor(s) Stadhouders R, Thongjuea S, Soler E
Citation(s) 24614105
Submission date Nov 21, 2013
Last update date May 15, 2019
Contact name Supat Thongjuea
Organization name The Weatherall Institute of Molecular Medicine
Department MRC Molecular Haematology Unit
Street address Headington
City Oxford
ZIP/Postal code OX3 9DS
Country United Kingdom
Platforms (2)
GPL9052 Illumina Genome Analyzer (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (8)
GSM1273197 LDB1 HEP
GSM1273198 Goat IgG HEP
BioProject PRJNA229562
SRA SRP033251

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Supplementary file Size Download File type/resource
GSE52637_RAW.tar 992.8 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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