Related Experiment Video
Updated: Nov 6, 2025
10:10
HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
Published on: March 31, 2019
8.5K
Single-nucleotide-level mapping of DNA regulatory elements that control fetal hemoglobin expression
Li Cheng1, Yichao Li1, Qian Qi1
1Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nature Genetics
|May 7, 2021
Summary
Researchers mapped noncoding DNA functions affecting fetal hemoglobin (HbF) expression. Targeting a novel repressor element increased HbF levels, offering potential therapeutic strategies for sickle cell disease (SCD).
Area of Science:
- Genetics
- Molecular Biology
- Genomics
Background:
- Functional noncoding DNA's role in health traits remains challenging to pinpoint.
- Fetal hemoglobin (HbF) expression is a genetically determined trait influencing sickle cell disease (SCD) severity.
Purpose of the Study:
- To develop a high-throughput framework for mapping noncoding DNA functions at single-nucleotide resolution.
- To investigate the genetic regulation of erythroid fetal hemoglobin (HbF) expression.
Main Methods:
- Utilized adenine base editor ABEmax to introduce A•T to G•C conversions in predicted regulatory elements.
- Quantified effects of these conversions on erythroid HbF expression.
- Integrated epigenomic data and linked regulatory elements to variants in an SCD cohort.
Main Results:
- Identified numerous functional regulatory elements controlling HbF expression.
- Defined epigenomic structures of these elements.
- Linked low-frequency variants to HbF expression in SCD patients.
Conclusions:
- Discovered a novel γ-globin gene repressor element.
- Demonstrated that targeting this element in hematopoietic progenitors increases HbF levels and inhibits sickling.
- Revealed complexities in HbF regulation with potential therapeutic implications for SCD.
More Related Videos
Related Concept Videos
01:30General Transcription Factors
6.1K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
6.1K
02:16Transcription Factors
80.1K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
80.1K
02:02Cis-regulatory Sequences
11.0K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.0K
02:23Master Transcription Regulators
7.3K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.3K
02:30Genomic Imprinting and Inheritance
35.9K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
35.9K