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

作者：Laurent Benoit; Randrianarison Huetz Voahangy; Frisan Emilie; Andrieu Soler Charlotte; Soler Eric; Fontenay Michaela; Dusanter Fourt Isabelle; Dumenil Dominique^*

来源：Journal of Cell Science, 2012, 125(4): 993-1002.

DOI：10.1242/jcs.095877

• Gfi-1B
• LSD1
• Erythroid differentiation
• Spliced variant
• Transcriptional repressor
• Isoform

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.

• 出版日期2012-2-15