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PreprintCited by 126Genomics and Chromatin DynamicsT-cell and B-cell ImmunologyCytokine Signaling Pathways and Interactions

Ets-related protein PU.1 regulates expression of the immunoglobulin J-chain gene through a novel Ets-binding element.

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Shin, M K, Koshland, M E·1993·Genes & Development
DOI 10.1101/gad.7.10.2006
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Abstract

In a primary immune response, a signal from interleukin-2 (IL-2) activates transcription of the gene encoding the pentamer IgM joining component, the J chain. Recently, a bifunctional control element (JB) in the J-chain promoter has been identified. This finding was pursued in the present study by purifying and characterizing the nuclear protein (NF-JB) that mediates the positive regulatory activity of the JB element. The analyses revealed that NF-JB is identical to the Ets-related B-cell- and macrophage-specific transcriptional factor, PU.1, despite the fact that the JB site lacks the GGA core reported to be essential for binding by members of the Ets oncoprotein family. The two factors were found to be indistinguishable with respect to their DNA-binding characteristics, size, and peptide structure. Moreover, in transient transfection assays, PU.1 alone activated reporter constructs containing the JB cis-element, and the activation was shown to be dependent on a glutamine-rich sequence in the amino-terminal portion of PU.1. Finally, a dominant negative mutant of PU.1 was capable of suppressing the transcriptional activity of a 1.2-kb J-chain promoter sequence. These results establish an important role for PU.1 in the regulation of immunoglobulin J-chain gene expression and provide new insights into the function(s) of the Ets transcription factors in lymphoid cells.

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Crossref · 10.1101/gad.7.10.2006

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  • J558L cells express the J chain gene, whose transcription has been suggested to be regulated by PU.1 binding to the J chain promoter.

    “J558L B cells also express the J chain gene, the transcription of which has been suggested to be regulated by PU.1 binding to the J chain promoter”

    From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Shin and Koshland, 1993

    The Discussion (page unavailable) reports that PU.1 binds a regulatory element in the J-chain promoter and activates J-chain transcription. The paper identifies S194 as a J-chain-expressing cell line, but the passages found do not establish that J558L cells express the gene; the cell-line-specific part of the claim is unsupported. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • J chain inhibition is presumably due to displacement of endogenous PU.1 from an isolated Ets site in the J chain promoter.

    “This is presumably due to displacement of endogenous PU.1 from an isolated Ets site in the J chain promoter”

    From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Shin and Koshland, 1993

  • HA/PU.1dlN133 has a dominant negative effect.

    “a vector expressing mutant PU.1 (HA/PU.1dlN133) that was previously shown to have a dominant negative effect (43).”

    From Interleukin-3 Stimulation of <i>mcl-1</i> Gene Transcription Involves Activation of the PU.1 Transcription Factor through a p38 Mitogen-Activated Protein Kinase-Dependent Pathway (2003) · cites this paper as [43]

  • Mutation of a PU.1 binding site just upstream of the FcγRIB gene transcriptional start abrogates myeloid expression, and replacing this mutant site with a TATA box re-establishes myeloid expression, indicating a positive feedback mechanism in PU.1 promoter regulation.

    “Evidently, mutation of a PU.1 binding site located just upstream of the transcriptional start site of the FcγRIB gene abrogates myeloid expression and replacement of this mutant site with a TATA box can re-establish myeloid expression indicating the presence of a positive feedback mechanism in the regulation of the PU.1 promoter [33].”

    From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [33]

  • For B-lymphoid genes such as Ig heavy chain, Ig light chains, mb-1, B29 and Ig-J chain, PU.1 binding to enhancers induces DNA bending that facilitates other transcription factors binding, forming a synergistic multiprotein complex that augments transcription.

    “In case of the B-lymphoid genes such as Ig heavy chain (μ) [34], Ig light chains (κ and λ) [35, 36], mb- (Ig α) [37], B29 (Ig β) [38] and Ig-J chain [33], the binding of PU.1 to the enhancer regions induces the bending of DNA that facilitates the binding of other transcription factors to their respective binding sites, thus forming a synergistic multiprotein-complex to augment transcription.”

    From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [33]

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Cites

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Research works printed but not linked: 3

  1. Baldwin, A.S. 1991. DNA-protein interactions. In Current pro- tocols in molecular bioIogy (ed. F.M. Ausubel, R. Brent, R.E. Kingston, D.D. Moore, J.G. Seidman, J.A. Smith, and K. Struhl), vol. 2, pp. 12.3.1-12.3.4. (Chap. 12}. Greene Publish- ing Associates, Brooklyn, New York.
  2. Chodosh, L.A. 1991. Chap. 12. DNA-protein interactions. In Current protocols in molecular biology (ed. F.M. Ausubel, R. Brent, R.E. Kingston, D.D. Moore, J.G. Seidman, J.A. Smith, and K. Struhl), vol. 2, pp. 12.5.1-.2.5.6 (Chap. 12). Greene Publishing Associates, Brooklyn, New York.
  3. Sambrook, J., E.F. Fritsch, and T. Maniatis. 1989. Molecular cloning: A laboratory manual. Cold Spring Harbor Labora- tory Press, Cold Spring Harbor, New York.

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Related

Authors
Shin, M. K., & Koshland, M. E.
Affiliations
University of California, Berkeley (US)
ORCID
Shin, M K
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
1993-10
Volume
7
Issue
10
Pages
2006-2015
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.7.10.2006
OpenAlex
W1996251228
Cited by
126
References
33
Citations by year
2021: 1 · 2019: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (AI 07079)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
PU.1, ETS transcription factors, interleukin-2 signaling, primary immune response, transcriptional regulation, dominant-negative mutant, B cells, macrophages, lymphoid cells
MeSH terms
Amino Acid Sequence, Base Sequence, DNA Mutational Analysis, DNA-Binding Proteins, Gene Expression Regulation, Multigene Family, Glutamine, Humans, Immunoglobulin J-Chains, Lymphoid Tissue, Molecular Sequence Data, Promoter Regions, Genetic, Structure-Activity Relationship, Transcription Factors, Transfection, Tumor Cells, Cultured, Transcriptional Activation, Retroviridae Proteins, Oncogenic, Genes, Reporter

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