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Roles of VWRPY motif‐mediated gene repression by Runx proteins during T‐cell development
Author(s) -
Seo Wooseok,
Tanaka Hirokazu,
Miyamoto Chizuko,
Leva Ditsa,
Groner Yoram,
Taniuchi Ichiro
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2012.6
Subject(s) - derepression , psychological repression , transcription factor , biology , gene silencing , runx1 , gene , genetics , microbiology and biotechnology , repressor , gene expression
Runx transcription factor family proteins have essential roles during T‐cell development by either activating or repressing target genes. For instance, lineage‐ and stage‐specific expression of Cd4 and ThPOK is controlled by a transcriptional silencer embedded in each locus, whose activity requires bindings of Runx complexes. The evolutionarily conserved VWRPY penta‐peptide sequences in Runx proteins have been shown to be responsible for repressive function as a platform to recruit Groucho/TLE transcriptional corepressors. However, it remains elusive whether requirement for the VWRPY motif differs among Runx target genes. By examining mice lacking VWRPY motifs in both Runx1 and Runx3 proteins, here, we show a full and partial derepression of Cd4 and ThPOK in CD8‐linegae T cells, respectively. Thus, whereas Cd4 silencing completely depends on the VWRPY motif, both VWRPY‐dependent and ‐independent mechanisms operate to repress ThPOK gene. These results indicate that Runx proteins utilize different modes to repress expression of different target genes.