Binding of Ikaros to the lambda5 promoter silences transcription through a mechanism that does not require heterochromatin formation.

Abstract

The Ikaros family of proteins are DNA binding factors required for correct development of B and T lymphocytes. Cytogenetic studies have shown that these proteins form complexes with pericentromeric heterochromatin in B cells, and the colocalization of transcriptionally silent genes with these complexes suggests that Ikaros could silence transcription by recruiting genes to heterochromatin. Here we show that a site in the lambda5 promoter that binds Ikaros and Aiolos is required for silencing of lambda5 expression in activated mature B cells. Analysis of methylation and nuclease accessibility indicates that the silenced lambda5 gene is not heterochromatinized in B cells, despite being associated with pericentromeric heterochromatin clusters. We also found that a promoter mutation, which affects Ikaros-mediated silencing of lambda5 expression, is not rescued in a transgenic line that has the gene integrated into pericentromeric heterochromatin. Our results indicate that the Ikaros proteins initiate silencing of lambda5 expression through a direct effect on the promoter with localization to pericentromeric heterochromatin likely to affect the action of Ikaros on regulatory sequences rather than causing heterochromatinization of the gene.

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@article{Sabbattini2001BindingOI, title={Binding of Ikaros to the lambda5 promoter silences transcription through a mechanism that does not require heterochromatin formation.}, author={Pierangela Sabbattini and Magnus Lundgren and Andrew Georgiou and C Chow and Gary Warnes and Niall Dillon}, journal={The EMBO journal}, year={2001}, volume={20 11}, pages={2812-22} }