Open AccessA short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1–CoREST complex through the dimethylation of its SNAG domain
Author(s) -
Laurent Beaugerie,
Voahangy Randrianarison-Huetz,
Emilie Frisan,
Charlotte Andrieu-Soler,
Éric Soler,
Michaëla Fontenay,
Isabelle DusanterFourt,
Dominique Duménil
Publication year - 2012
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.095877
Subject(s) - biology , gene isoform , repressor , alternative splicing , erythropoiesis , microbiology and biotechnology , exon , gene , rna splicing , genetics , transcription factor , medicine , rna , anemia
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.