3'HS1 CTCF binding site in human β-globin locus regulates fetal hemoglobin expression
- Van Andel Institute, United States
- The University of Michigan, United States
- Japanese Red Cross Society, Japan
- RIKEN BioResource Center, Japan
Abstract
Mutations in the adult β-globin gene can lead to a variety of hemoglobinopathies, including sickle cell disease and β-thalassemia. An increase in fetal hemoglobin expression throughout adulthood, a condition named Hereditary Persistence of Fetal Hemoglobin (HPFH), has been found to ameliorate hemoglobinopathies. Deletional HPFH occurs through the excision of a significant portion of the 3' end of the β-globin locus, including a CTCF binding site termed 3'HS1. Here, we show that the deletion of this CTCF site alone induces fetal hemoglobin expression in both adult CD34+ hematopoietic stem and progenitor cells and HUDEP-2 erythroid progenitor cells. This induction is driven by the ectopic access of a previously postulated distal enhancer located in the OR52A1 gene downstream of the locus, which can also be insulated by the inversion of the 3'HS1 CTCF site. This suggests that genetic editing of this binding site can have therapeutic implications to treat hemoglobinopathies.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE160425.
Article and author information
Author details
Funding
National Human Genome Research Institute (1R35HG011279-01)
- Jie Liu
Van Andel Research Institute (Fellow program)
- Xiaotian Zhang
American Society of Hematology (Scholar Program)
- Xiaotian Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Michael D Bulger, University of Rochester, United States
Version history
- Preprint posted: May 18, 2021 (view preprint)
- Received: May 21, 2021
- Accepted: September 22, 2021
- Accepted Manuscript published: September 29, 2021 (version 1)
- Version of Record published: October 8, 2021 (version 2)
Copyright
© 2021, Himadewi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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3'HS1 CTCF binding site in human β-globin locus regulates fetal hemoglobin expression
eLife 10:e70557.
https://doi.org/10.7554/eLife.70557
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