A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1–CoREST complex through the dimethylation of its SNAG domain

• DOI: 10.1242/jcs.095877
• Publication Date: 2012-03-08T03:39:14Z
• Authors: Benoît Laurent; Voahangy Randrian...; Emilie Frisan; Charlotte Andrieu...; Eric Soler; Michaela Fontenay; Isabelle Dusanter...; Dominique Duménil
• Keywords: Histone Demethylases; 0301 basic medicine; Lysine; Amino Acid Motifs; Gene Expression Regulation, Developmental; Nerve Tissue Proteins; Zinc Fingers; Methylation; Cell Line; Protein Structure, Tertiary; Molecular Weight; Repressor Proteins; Alternative Splicing; 03 medical and health sciences; Proto-Oncogene Proteins; Humans; Protein Isoforms; Erythropoiesis; Promoter Regions, Genetic; Co-Repressor Proteins; Erythropoietin; Protein Binding

Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis. Here we identify p32, isoform, as erythroid differentiation. p32 generated by alternative splicing lacks two first zinc finger domains protein. Selective knock down compromises differentiation, whereas its ectopic expression induces in absence erythropoietin. isoform binds to target gene promoters associates with LSD1–CoREST complex more efficiently than major p37 isoform. Furthermore, show that includes KSKK motif SNAG domain, which recruits only when dimethylated on lysine 8. Mutation 8 prevents p32-induced development. Our results thus highlight key role alternatively spliced