title: MafG sumoylation is required for active transcriptional repression.
abstract: A straightforward mechanism for eliciting transcriptional repression would be to simply block the DNA binding site for activators. Such passive repression is often mediated by transcription factors that lack an intrinsic repressor activity. MafG is a bidirectional regulator of transcription, a repressor in its homodimeric state but an activator when heterodimerized with p45. Here, we report that MafG is conjugated to SUMO-2/3 in vivo. To clarify the possible physiological role(s) for sumoylation in regulating MafG activity, we evaluated mutant and wild-type MafG in transgenic mice and cultured cells. Whereas sumoylation-deficient MafG activated p45-dependent transcription normally and did not affect heterodimer activity, repression by the sumoylation-deficient MafG mutant was severely compromised in vivo. Furthermore, the SUMO-dependent repression activity of MafG was sensitive to histone deacetylase inhibition. Thus, repression by MafG is not achieved through simple passive repression by competing for the activator binding site but requires sumoylation, which then mediates transcriptional repression through recruitment of a repressor complex containing histone deacetylase activity.
authors.affiliation: Graduate School of Comprehensive Human Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan. hozumim@tara.tsukuba.ac.jp
authors.forename: Hozumi
authors.initials: H
authors.lastname: Motohashi
authors.forename: Fumiki
authors.initials: F
authors.lastname: Katsuoka
authors.forename: Chika
authors.initials: C
authors.lastname: Miyoshi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uchimura
authors.forename: Hisato
authors.initials: H
authors.lastname: Saitoh
authors.forename: Claire
authors.initials: C
authors.lastname: Francastel
authors.forename: James Douglas
authors.initials: JD
authors.lastname: Engel
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D015342:DNA Probes / Q000235:genetics; D019281:Dimerization; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000737:chemistry; D051259:MafG Transcription Factor / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050985:MafK Transcription Factor / Q000235:genetics / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D008969:Molecular Sequence Data; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D015342:DNA Probes; D051259:MafG Transcription Factor; D050985:MafK Transcription Factor; C491247:Mafg protein, mouse; C494696:Mafk protein, mouse; C414349:Piasy protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011994:Recombinant Proteins; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D006655:Histone Deacetylases; D008239:Lysine