The promoter of the Immunoglobulin J Chain gene receives its authentic enhancer activity through the abutting MEF2 and PU.1 sites in a DNA-looping interaction.
Immunoglobulin J chain (IgJ) promoter had previously been dissected in the context of a heterologous enhancer and/or promoter because its strength was weak and its authentic enhancer was not available at that time. Thus, it has been questioned whether the previous dissection of the IgJ promoter might also be relevant in the context of its authentic enhancer. Now that the authentic IgJ enhancer has been identified, redelineation of the IgJ promoter could be performed in the context of this authentic enhancer. In this redelineation, the previously identified MEF2 and PU.1 sites were shown to be critical for communicating with its authentic enhancer and thereby for receiving enhancer activity. In accordance with this finding, a DNA-looping interaction between the IgJ promoter and its enhancer was demonstrated using chromosome conformation capture assays not only in IgJ-expressing S194 plasma cells but also during interleukin-2-induced BCL1 B-cell terminal differentiation. Furthermore, MEF2 was shown to be reciprocally coimmunoprecipitated with E47, which had been identified to bind to the IgJ enhancer, suggesting that the DNA-looping interaction between the IgJ promoter and its enhancer might be mediated by these proteins. However, the previously identified USF and BSAP sites were shown to be not important for IgJ promoter activity in the context of its authentic enhancer. These findings were further supported by in vivo footprinting and/or chromatin immunoprecipitation assays, which showed the binding of MEF2 and PU.1-but not the binding of USF and BSAP-to the IgJ promoter.
Lim
Jung-Hyun
JH
Institute of Life Science and Resources, Kyung Hee University, Seocheon, Giheung, Yongin, Gyeonggi-do, Republic of Korea.
Kim
Hong-Gi
HG
Park
Sung-Kyun
SK
Kang
Chang-Joong
CJ
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D010950:Plasma Cells / Q000502:physiology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051820:TCF Transcription Factors / Q000378:metabolism; D058125:Transcription Factor 7-Like 1 Protein
D007144:Immunoglobulin J-Chains; D018006:Myogenic Regulatory Factors; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein