title: Roles of VWRPY motif-mediated gene repression by Runx proteins during T-cell development.
abstract: 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.
authors.affiliation: Laboratory for Transcriptional Regulation, Research Center for Allergy and Immunology, RIKEN, Yokohama, Kanagawa, Japan.
authors.forename: Wooseok
authors.initials: W
authors.lastname: Seo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Chizuko
authors.initials: C
authors.lastname: Miyamoto
authors.forename: Ditsa
authors.initials: D
authors.lastname: Levanon
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000737:chemistry* / Q000378:metabolism*; D050677:Core Binding Factor Alpha 3 Subunit / Q000737:chemistry* / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D014157:Transcription Factors; C493726:Runx1 protein, mouse; C493730:Runx3 protein, mouse; C497211:Zbtb7b protein, mouse