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Cited by 125Genomics and Chromatin DynamicsHemoglobinopathies and Related DisordersChromatin Remodeling and Cancer

Role of LDB1 in the transition from chromatin looping to transcription activation

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Krivega, Ivan, Dale, Ryan K., Dean, Ann·2014·Genes & Development
DOI 10.1101/gad.239749.114PMC PMC4066399
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Abstract

Many questions remain about how close association of genes and distant enhancers occurs and how this is linked to transcription activation. In erythroid cells, lim domain binding 1 (LDB1) protein is recruited to the β-globin locus via LMO2 and is required for looping of the β-globin locus control region (LCR) to the active β-globin promoter. We show that the LDB1 dimerization domain (DD) is necessary and, when fused to LMO2, sufficient to completely restore LCR–promoter looping and transcription in LDB1-depleted cells. The looping function of the DD is unique and irreplaceable by heterologous DDs. Dissection of the DD revealed distinct functional properties of conserved subdomains. Notably, a conserved helical region (DD4/5) is dispensable for LDB1 dimerization and chromatin looping but essential for transcriptional activation. DD4/5 is required for the recruitment of the coregulators FOG1 and the nucleosome remodeling and deacetylating (NuRD) complex. Lack of DD4/5 alters histone acetylation and RNA polymerase II recruitment and results in failure of the locus to migrate to the nuclear interior, as normally occurs during erythroid maturation. These results uncouple enhancer–promoter looping from nuclear migration and transcription activation and reveal new roles for LDB1 in these processes.

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  • LDB1 forms loops independently of both cohesin and CTCF.

    “In contrast to YY1 and ZNF143, LDB1 has been shown to form loops independently of both cohesin and CTCF [371, 375].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [375]

    The Abstract and Results (Figure 3; page not specified) show that LDB1 and its dimerization domain support β-globin LCR–promoter looping. They do not establish that this looping is independent of cohesin or CTCF; the paper discusses those proteins as factors in other looping mechanisms. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Krivega, I., Dale, R. K., & Dean, A.
Affiliations
National Institutes of Health (US)
Corresponding author
Dean, Ann
ORCID
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
2014-05-29
Volume
28
Issue
12
Pages
1278-1290
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.239749.114
PMC
PMC4066399
OpenAlex
W2114438477
Cited by
125
References
11
Citations by year
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Type
posted content
Language
en
Open access
Licence
cc-by-nc
Locations
  • Genes & Development (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK015508, ZIADK015508)
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 › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
LDB1, LMO2, chromatin looping, enhancer-promoter looping, transcriptional activation, beta-globin locus control region, erythroid cells, FOG-1, NuRD complex, histone acetylation, RNA polymerase II recruitment, nuclear migration
MeSH terms
Animals, Cell Nucleus, Cells, Cultured, Chromatin, DNA-Binding Proteins, Nuclear Proteins, Transcription Factors, Transcriptional Activation, Gene Deletion, Dimerization, Erythroid Cells, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice, beta-Globins, LIM Domain Proteins

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