Eos and Pegasus, Two Members of the Ikaros Family of Proteins with Distinct DNA Binding Activities

José Perdomo,Melissa Holmes,Beng Chong,Merlin Crossley

doi:10.1074/jbc.m005457200

José Perdomo, Melissa Holmes + Show 2 more

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https://doi.org/10.1074/jbc.m005457200

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Abstract

Members of the Ikaros family of transcription factors, Ikaros, Aiolos, and Helios, are expressed in lymphocytes and have been implicated in controlling lymphoid development. These proteins contain two characteristic clusters of zinc fingers, an N-terminal domain important for DNA recognition, and a C-terminal domain that mediates homo- and heterotypic associations between family members. The conservation of these domains is such that all three proteins recognize related DNA sequences, and all are capable of dimerizing with other family members. Here we describe two additional Ikaros family proteins, Eos and Pegasus. Eos is most highly related to Helios and shares its DNA binding and protein association properties. Pegasus is related to other Ikaros proteins in its C-terminal dimerization domain but contains a divergent N-terminal zinc finger domain. Pegasus self-associates and binds to other family members but recognizes distinct DNA-binding sites. Eos and Pegasus repress the expression of reporter genes containing their recognition elements. Our results suggest that these proteins may associate with previously described Ikaros family proteins in lymphoid cells and play additional roles in other tissues.

Highlights

Members of the Ikaros family of transcription factors, Ikaros, Aiolos, and Helios, are expressed in lymphocytes and have been implicated in controlling lymphoid development
It has been shown that mutant Ikaros isoforms, containing only the C-terminal dimerization domain, behave as dominant negative mutants that impair the ability of Ikaros to activate transcription in cellular assays [6] and give rise to an aggressive form of lymphoblastic leukemia in mice [4]
Two partial clones encoding zinc fingers related to the C-terminal fingers of Ikaros family proteins were identified

Summary

Introduction

Members of the Ikaros family of transcription factors, Ikaros, Aiolos, and Helios, are expressed in lymphocytes and have been implicated in controlling lymphoid development These proteins contain two characteristic clusters of zinc fingers, an N-terminal domain important for DNA recognition, and a C-terminal domain that mediates homo- and heterotypic associations between family members. The conservation of these domains is such that all three proteins recognize related DNA sequences, and all are capable of dimerizing with other family members. Because the C-terminal zinc fingers of any Ikaros isoform can mediate interactions with any other Ikaros isoform [7] or with additional Ikaros family members (see below) and potentially influence their DNA binding and transcriptional properties, the precise mechanism by which these dominant negative mutants function in vivo has not been easy to determine

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