The chicken immunoglobulin lambda light chain gene is transcriptionally controlled by a modularly organized enhancer and an octamer-dependent silencer

鸡免疫球蛋白λ轻链基因的转录受模块化增强子和八聚体依赖性沉默子的调控。

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Abstract

Characterization of the regulatory elements involved in V(D)J recombination is crucial for understanding development of the B and T cell immune repertoire. Previously we have shown that the chicken immunoglobulin lambda light chain gene (CLLCG) undergoes lymphoid-specific rearrangement in transgenic mice. The whole gene is only 10 kb in length and contains all phylogenetically conserved target sites for recombinational and transcriptional regulation. In this study we have localized an enhancer element in a region 4 kb downstream of the constant (C) region. The 467 bp element can be subdivided into three subfragments. The previously detected silencer element on the V-J intervening sequence is shown to be localized on a 500 bp fragment. Partial silencer activity is retained on a 250 bp fragment, which includes an octamer motif. By mutational analysis this octamer is shown to be essential for B cell- but not for T cell-specific silencer function. The silencer represses transcription directed by heterologous elements like the SV 40 promoter or the Ig kappa 3' enhancer. We propose that transcription of the unrearranged and rearranged Ig genes is regulated by complex interactions between different modules from the promoter, enhancer and silencer, which is eliminated by recombination during B cell development.

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