Yin Yang 1 is a lipopolysaccharide-inducible activator of the murine 3′ Igh enhancer, hs3

Steven J. Gordon, Shireen Saleque, Barbara K. Birshtein

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The 3′ Igh enhancers, DNase I hypersensitive site (hs) 3B and/or hs4, are required for germline transcription, and hence, class switch recombination for multiple isotypes. A number of hs3-binding transcription factors have been identified by EMSA, including octamer and NF-κB family members, and Pax5. We have found that the binding of the transcription factor, Yin Yang 1 (YY1), to hs3 and to the μE1 site of the intronic enhancer, Eμ, is induced in primary splenic B cells after ∼48 h in response to LPS and other activators of class switch recombination. Transient transfection experiments in B cell lines indicate that YY1 is an activator of hs3. Interestingly, levels of YY1 expression are unchanged in resting and LPS-stimulated B cells. Mixing experiments followed by EMSA showed that a protein present in resting B cells prevented binding of YY1 to DNA. We found that recombinant retinoblastoma protein (Rb) inhibited binding of YY1 to hs3 in a dose-dependent manner, and we have identified complexes of endogenous YY1 with the Rb in resting B cells, but not in LPS-stimulated B cells. A difference in Rb phosphorylation state was also confirmed between resting (Go) B cells and LPS-stimulated B cells. These observations suggest that the interaction of YY1 with hypophosphorylated Rb in resting B cells prevents interaction of YY1 with DNA. After stimulation with class-switching activators, such as LPS, Rb becomes hyperphosphorylated and YY1 is released and can then bind to the hs3 enhancer and Eμ.

Original languageEnglish (US)
Pages (from-to)5549-5557
Number of pages9
JournalJournal of Immunology
Volume170
Issue number11
StatePublished - Jun 1 2003

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Yin-Yang
Lipopolysaccharides
B-Lymphocytes
Genetic Recombination
Transcription Factors
Immunoglobulin Class Switching
Retinoblastoma Protein
Deoxyribonuclease I
DNA
Recombinant Proteins
Cell Communication
Transfection
Phosphorylation

ASJC Scopus subject areas

  • Immunology

Cite this

Gordon, S. J., Saleque, S., & Birshtein, B. K. (2003). Yin Yang 1 is a lipopolysaccharide-inducible activator of the murine 3′ Igh enhancer, hs3. Journal of Immunology, 170(11), 5549-5557.

Yin Yang 1 is a lipopolysaccharide-inducible activator of the murine 3′ Igh enhancer, hs3. / Gordon, Steven J.; Saleque, Shireen; Birshtein, Barbara K.

In: Journal of Immunology, Vol. 170, No. 11, 01.06.2003, p. 5549-5557.

Research output: Contribution to journalArticle

Gordon, SJ, Saleque, S & Birshtein, BK 2003, 'Yin Yang 1 is a lipopolysaccharide-inducible activator of the murine 3′ Igh enhancer, hs3', Journal of Immunology, vol. 170, no. 11, pp. 5549-5557.
Gordon, Steven J. ; Saleque, Shireen ; Birshtein, Barbara K. / Yin Yang 1 is a lipopolysaccharide-inducible activator of the murine 3′ Igh enhancer, hs3. In: Journal of Immunology. 2003 ; Vol. 170, No. 11. pp. 5549-5557.
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