Cited by 131Genomics and Chromatin DynamicsHemoglobinopathies and Related DisordersGenetic Associations and Epidemiology

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Chapter 4 β‐Globin Regulation and Long‐Range Interactions

Palstra, Robert‐Jan, de Laat, Wouter, Grosveld, Frank·2008·Advances in genetics

DOI 10.1016/s0065-2660(07)00004-1

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Abstract

Transcriptional activation in higher eukaryotes frequently involves the long-range action of a number of regulatory DNA elements. One of the main questions in transcriptional regulation is how cis-regulatory elements communicate with the promoter of a gene over large distances. There has been a lively debate in recent years whether this communication takes place via a noncontact mechanism (linking, tracking) or via a contact mechanism (looping). The demonstration that the major regulatory element of the beta-globin locus, the locus control region (LCR), is in close proximity to the active beta-globin genes validates the contact model for long-range activation. Here, we will review the beta-globin locus as a model system to study long-range activation, briefly describe the different models for long-range activation, and summarize the recent findings that the LCR of the beta-globin locus is in close proximity to the active promoters. Although it is now firmly established that looping takes place within the beta-globin locus (and other loci), it is not clear how these long-range contacts are established and what the precise role is of the LCR. We will argue that the main action of the LCR takes place at the promoter and open reading frame of the gene itself and we will discuss key rate-limiting steps in transcriptional activation and the possible mechanisms by which they are influenced by the LCR.

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See all 131

Authors: Palstra, R., de Laat, W., & Grosveld, F.
Affiliations: Erasmus MC (NL)
ORCID: Palstra, Robert‐Jan
Grosveld, Frank
Venue: Advances in genetics
Publisher: Elsevier
Published: 2008
Volume: 61
Pages: 107-142
ISSN: 0065-2660 (ISSN-L)
DOI: 10.1016/s0065-2660(07)00004-1
OpenAlex: W1564263074
Cited by: 131
References: 180
Citations by year: 2026: 1 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 7 · 2016: 4 · 2015: 6 · 2014: 8 · 2013: 8 · 2012: 15
FWCI: 23.68
Type: book chapter
Language: en
Open access: closed
Locations: Advances in genetics (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: beta-globin locus, locus control region, chromatin looping, cis-regulatory elements, transcriptional regulation, gene expression regulation
MeSH terms: Animals, Chromatin, Epistasis, Genetic, Gene Expression Regulation, Globins, Humans, Models, Biological, Promoter Regions, Genetic, Transcription, Genetic, Locus Control Region, Gene Order

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Chapter 4 β‐Globin Regulation and Long‐Range Interactions

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