ArticleGenes & development2003
The beta -globin locus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation.
Article in Genes & development, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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91 citing papers in PubMed, 164 citations in OpenAlex.
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- Mechanisms of enhancer action: the known and the unknown.Genome biology · 2021Review
- Evidence for additive and synergistic action of mammalian enhancers during cell fate determination.eLife · 2021Article
- Enhancers predominantly regulate gene expression during differentiation via transcription initiation.Molecular cell · 2021Article
- Super-enhancer mediated regulation of adult β-globin gene expression: the role of eRNA and Integrator.Nucleic acids research · 2021Article
- Erythropoietin Regulates Transcription and YY1 Dynamics in a Pre-established Chromatin Architecture.iScience · 2020Article
- Enhancer RNAs are an important regulatory layer of the epigenome.Nature structural & molecular biology · 2020Review
- MicroRNA-196a is regulated by ER and is a prognostic biomarker in ER+ breast cancer.British journal of cancer · 2019Article
- Phase Separation and Transcription Regulation: Are Super-Enhancers and Locus Control Regions Primary Sites of Transcription Complex Assembly?BioEssays : news and reviews in molecular, cellular and developmental biology · 2019Review
- Genome-Wide Maps of Transcription Regulatory Elements and Transcription Enhancers in Development and Disease.Comprehensive Physiology · 2018Review
- Eukaryotic core promoters and the functional basis of transcription initiation.Nature reviews. Molecular cell biology · 2018Review
- Gene Therapy for β-Hemoglobinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Effect of Interaction between Chromatin Loops on Cell-to-Cell Variability in Gene Expression.PLoS computational biology · 2016Article
- Enhancer Regulation of Transcriptional Bursting Parameters Revealed by Forced Chromatin Looping.Molecular cell · 2016Article
- High Fractional Occupancy of a Tandem Maf Recognition Element and Its Role in Long-Range β-Globin Gene Regulation.Molecular and cellular biology · 2016Article
- Long-Range Chromatin Interactions.Cold Spring Harbor perspectives in biology · 2015Review
- Dynamic enhancer-gene body contacts during transcription elongation.Genes & development · 2015Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
To investigate the molecular basis of beta-globin gene activation, we analyzed factor recruitment and histone modification at the adult beta-globin gene in wild-type (WT)/locus control region knockout (DeltaLCR) heterozygous mice and in murine erythroleukemia (MEL) cells. Although histone acetylation and methylation (Lys 4) are high before and after MEL differentiation, recruitment of the erythroid-specific activator NF-E2 to the promoter and preinitiation complex (PIC) assembly occur only after differentiation. We reported previously that targeted deletion of the LCR reduces beta-globin gene expression to 1%-4% of WT without affecting promoter histone acetylation. Here, we report that NF-E2 is recruited equally efficiently to the adult beta-globin promoters of the DeltaLCR and WT alleles. Moreover, the LCR deletion reduces PIC assembly only twofold, but has a dramatic effect on Ser 5 phosphorylation of RNA polymerase II and transcriptional elongation. Our results suggest at least three distinct stages in beta-globin gene activation: (1) an LCR-independent chromatin opening stage prior to NF-E2 recruitment to the promoter and PIC assembly; (2) an intermediate stage in which NF-E2 binding (LCR-independent) and PIC assembly (partially LCR-dependent) occur; and (3) an LCR-dependent fully active stage characterized by efficient pol II elongation. Thus, in its native location the LCR functions primarily downstream of activator recruitment and PIC assembly.
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