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Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation
Author(s) -
Morgan Bruce,
Sun Lei,
Avitahl Nicole,
Andrikopoulos Konstantinos,
Ikeda Tohru,
Gonzales Ellen,
Wu Paul,
Neben Steve,
Georgopoulos Katia
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.8.2004
Subject(s) - biology , transcription factor , genetics , microbiology and biotechnology , phenotype , gene
Development of the lymphoid system is dependent on the activity of zinc finger transcription factors encoded by the Ikaros gene. Differences between the phenotypes resulting from a dominant‐negative and a null mutation in this gene suggest that Ikaros proteins act in concert with another factor with which they form heterodimers. Here we report the cloning of Aiolos , a gene which encodes an Ikaros homologue that heterodimerizes with Ikaros proteins. In contrast to Ikaros_which is expressed from the pluripotent stem cell to the mature lymphocyte_Aiolos is first detected in more committed progenitors with a lymphoid potential and is strongly up‐regulated as these differentiate into pre‐T and pre‐B cell precursors. The expression patterns of Aiolos and Ikaros, the relative transcriptional activity of their homo‐ and heteromeric complexes, and the dominant interfering effect of mutant Ikaros isoforms on Aiolos activity all strongly suggest that Aiolos acts in concert with Ikaros during lymphocyte development. We therefore propose that increasing levels of Ikaros and Aiolos homo‐ and heteromeric complexes in differentiating lymphocytes are essential for normal progression to a mature and immunocompetent state.