title: A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain.
abstract: Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis. Here we identify Gfi-1B p32, a Gfi-1B isoform, as essential for erythroid differentiation. Gfi-1B p32 is generated by alternative splicing and lacks the two first zinc finger domains of the protein. Selective knock down of Gfi-1B p32 compromises erythroid differentiation, whereas its ectopic expression induces erythropoiesis in the absence of erythropoietin. Gfi-1B p32 isoform binds to Gfi-1B target gene promoters and associates with the LSD1-CoREST repressor complex more efficiently than the major Gfi-1B p37 isoform. Furthermore, we show that Gfi-1B includes a KSKK motif in its SNAG domain, which recruits the repressor complex only when dimethylated on lysine 8. Mutation of lysine 8 prevents Gfi-1B p32-induced erythroid development. Our results thus highlight a key role for the alternatively spliced Gfi-1B p32 isoform in erythroid development.
authors.affiliation: Institut Cochin, Université Paris Descartes, Paris Sorbonne Cité, CNRS (UMR 8104), Paris,  France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Laurent
authors.forename: Voahangy
authors.initials: V
authors.lastname: Randrianarison-Huetz
authors.forename: Emilie
authors.initials: E
authors.lastname: Frisan
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andrieu-Soler
authors.forename: Eric
authors.initials: E
authors.lastname: Soler
authors.forename: Michaela
authors.initials: M
authors.lastname: Fontenay
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dusanter-Fourt
authors.forename: Dominique
authors.initials: D
authors.lastname: Duménil
mesh_terms: D017398:Alternative Splicing; D020816:Amino Acid Motifs; D002460:Cell Line; D056970:Co-Repressor Proteins; D004920:Erythropoiesis / Q000235:genetics; D004921:Erythropoietin; D018507:Gene Expression Regulation, Developmental; D056466:Histone Demethylases / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D056970:Co-Repressor Proteins; C111977:GFI1B protein, human; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; C121019:RCOR1 protein, human; D012097:Repressor Proteins; D004921:Erythropoietin; D056466:Histone Demethylases; C495195:KDM1A protein, human; D008239:Lysine