Yin Yang 1 is a lipopolysaccharide-inducible activator of the murine 3' Igh enhancer, hs3.
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-kappa B family members, and Pax5. We have found that the binding of the transcription factor, Yin Yang 1 (YY1), to hs3 and to the mu E1 site of the intronic enhancer, E mu, is induced in primary splenic B cells after approximately 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 (G(0)) 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 E mu.
Gordon
Steven J
SJ
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Saleque
Shireen
S
Birshtein
Barbara K
BK
D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D001667:Binding, Competitive / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000502:physiology; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism / Q000494:pharmacology; D015534:Trans-Activators / Q000096:biosynthesis / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D050986:YY1 Transcription Factor
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D007143:Immunoglobulin Heavy Chains; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D003850:Deoxyribonuclease I