Journal
JOURNAL OF CELL SCIENCE
Volume 125, Issue 4, Pages 993-1002Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.095877
Keywords
Gfi-1B; LSD1; Erythroid differentiation; Spliced variant; Transcriptional repressor; Isoform
Categories
Funding
- INSERM, Paris, France
- Fondation de France [20007002071]
- Association pour la Recherche sur le Cancer (ARC)
- Societe Franeaise d'Hematlogie (SFH)
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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.
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