A positive role for NLI/Ldb1 in long-range β-globin locus control region function

Song, Sang-Hyun; Hou, Chunhui; Dean, Ann

doi:10.1016/j.molcel.2007.09.025

Cited by 233Genomics and Chromatin DynamicsHemoglobinopathies and Related DisordersHemoglobin structure and function

A positive role for NLI/Ldb1 in long-range β-globin locus control region function

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Song, Sang-Hyun, Hou, Chunhui, Dean, Ann·2007·Molecular Cell

DOI 10.1016/j.molcel.2007.09.025PMC PMC2195932

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Abstract

Long-range interactions between distant regulatory elements, such as enhancers, and their target genes underlie the specificity of gene expression in many developmentally regulated gene families. NLI/Ldb1, a widely expressed nuclear factor, is a potential mediator of long-range interactions. Here, we show that NLI/Ldb1 and erythroid-binding partners GATA-1/SCL/LMO2 bind in vivo to the beta-globin locus control region (LCR). The C-terminal LIM interaction domain of NLI is required for formation of the complex on chromatin. Loss of the LIM domain converts NLI into a dominant-negative inhibitor of globin gene expression, and knockdown of NLI by using shRNA results in failure to activate beta-globin expression. Kinetic studies reveal that the NLI/GATA-1/SCL/LMO2 complex is detected at the beta-globin promoter coincident with RNA Pol II recruitment, beta-globin transcription, and chromatin loop formation during erythroid differentiation, providing evidence that NLI facilitates long-range gene activation.

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Several TFs were required for looping between the LCR and the distal genes, including GATA-1, FOG-1, EKLF and NLI/Ldb1.
“Following the discovery of chromatin looping in the β-globin locus, it was ascertained that several TFs were required for looping between the LCR and the distal genes, including GATA-1, FOG-1, EKLF and NLI/Ldb1 [315–317].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [317]
LDB1 was first identified as a looping factor in the mouse β-globin locus.
“LDB1 was first identified as a looping factor in the mouse β-globin locus [317, 371].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [317]
In adult type murine erythroid cells, Ldb1 is required for the juxtaposition between the LCR and the adult β-major globin gene.
“In adult type murine erythroid cells, Ldb1 is required for the juxtaposition between the LCR and the adult β-major globin gene (Deng et al., 2012; Song et al., 2007).”
From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Song et al., 2007

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RED CELLS, IRON, AND ERYTHROPOIESIS Distinct Ldb1/NLI complexes orchestrate -globin repression and reactivation through ETO2 in human adult erythroid cells
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Authors: Song, S.-H., Hou, C., & Dean, A.
Affiliations: National Institutes of Health (US)
Corresponding author: Dean, Ann
ORCID: Song, Sang-Hyun
Hou, Chunhui
Dean, Ann
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2007-12
Volume: 28
Issue: 5
Pages: 810-822
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/j.molcel.2007.09.025
PMC: PMC2195932
OpenAlex: W2015584675
Cited by: 233
References: 59
Citations by year: 2026: 4 · 2025: 11 · 2024: 6 · 2023: 10 · 2022: 7 · 2021: 6 · 2020: 11 · 2019: 12 · 2018: 12 · 2017: 13 · 2016: 16 · 2015: 22 · 2014: 17 · 2013: 17 · 2012: 14
FWCI: 5.29
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2055 d)
Locations: Molecular Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (Z01DK015508)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords: beta-globin locus control region, long-range enhancer-promoter interactions, GATA-1, SCL, LMO2, LIM domain, chromatin looping, erythroid differentiation, RNA polymerase II recruitment, dominant negative inhibition, transcriptional activation
MeSH terms: T-Cell Acute Lymphocytic Leukemia Protein 1, Cell Differentiation, Chromatin, DNA-Binding Proteins, Gene Expression Regulation, Globins, Humans, Kinetics, Metalloproteins, Promoter Regions, Genetic, Proto-Oncogene Proteins, Regulatory Sequences, Nucleic Acid, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, Immunoblotting, Transcriptional Activation, Locus Control Region, RNA, Small Interfering, Erythroid Cells, Chromatin Immunoprecipitation, Immunoprecipitation, Adaptor Proteins, Signal Transducing, GATA1 Transcription Factor, Basic Helix-Loop-Helix Proteins, LIM Domain Proteins

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A positive role for NLI/Ldb1 in long-range β-globin locus control region function

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