Each hypersensitive site of the human beta-globin locus control region confers a different developmental pattern of expression on the globin genes

Fraser, P; Pruzina, S; Antoniou, M; Grosveld, F

doi:10.1101/gad.7.1.106

Cited by 236Hemoglobinopathies and Related DisordersGenomics and Chromatin DynamicsHemoglobin structure and function

Each hypersensitive site of the human beta-globin locus control region confers a different developmental pattern of expression on the globin genes

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Fraser, P, Pruzina, S, Antoniou, M, Grosveld, F·1993·Genes & Development

DOI 10.1101/gad.7.1.106

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Abstract

We have tested the effect of the individual DNase I hypersensitive site (HS) regions of the globin locus control region (LCR) on the developmental expression pattern of the human gamma and beta genes in transgenic mice. The results show that HS3 is the most active site during the embryonic period. It is also the only site capable of high level expression of the gamma genes during fetal hematopoiesis, in a population of cells that are capable of expressing both the gamma and beta genes. Region HS4 shows the highest activity during the adult stage and expresses the gamma genes only at low levels during the embryonic period. HS2 drives equivalent levels of gamma or beta transgene expression throughout development. HS1 has a similar pattern to HS2, although the activity of HS1 is very low. From these results we conclude that the HS regions have distinct developmental specificities and suggest that in the complete LCR they interact with each other to form a larger complex which, in turn, interacts with the globin genes.

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HS1 has no intrinsic enhancer activity in embryonic, fetal, or adult erythropoiesis.
“when tested individually, HS1 has no intrinsic enhancer activity in embryonic, fetal, or adult erythropoiesis;45”
From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [45]
The HS1 transgenic-line results (Fig. 3; page unavailable in our copy) report expression above the comparison lines in the embryonic yolk sac, fetal liver, and adult blood. The paper concludes that HS1 has very weak activity, not no activity; the Abstract likewise describes its activity as very low. (LLM, conf=0.95)
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Authors: Fraser, P., Pruzina, S., Antoniou, M., & Grosveld, F.
Affiliations: National Institute for Medical Research (GB)
ORCID: Fraser, P
Antoniou, M
Grosveld, F
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 1993-01
Volume: 7
Issue: 1
Pages: 106-113
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.7.1.106
OpenAlex: W2083295035
Cited by: 231
References: 28
Citations by year: 2025: 3 · 2024: 11 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 5 · 2012: 3
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed (publishedVersion)
Funders: Medical Research Council
Topics: Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords: beta-globin locus control region, DNase I hypersensitive sites, globin gene expression, developmental gene regulation, gamma-globin gene, beta-globin gene, fetal hematopoiesis, embryonic gene expression, transgenic mice
MeSH terms: Animals, Cloning, Molecular, Embryonic and Fetal Development, Gene Expression Regulation, Globins, Humans, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Regulatory Sequences, Nucleic Acid, Mice

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Each hypersensitive site of the human beta-globin locus control region confers a different developmental pattern of expression on the globin genes

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